University of North Florida
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Stuart Chalk, Ph.D.
Department of Chemistry
University of North Florida
Phone: 1-904-620-1938
Fax: 1-904-620-3535
Email: schalk@unf.edu
Website: @unf

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Pharmaceutical

Classification: Pharmaceutical

Citations 452

"Spectrophotometric And Spectrofluorimetric Determination Of Famotidine And Ranitidine Using 1,4-benzoquinone Reagent"
Anal. Lett. 1999 Volume 32, Issue 7 Pages 1403-1419
Abdel Kader S. Ahmad; M. Abdel Kawy; M. Nebsen

Abstract: Spectrophotometric and spectrofluorimetric methods were adopted for the analysis of Famotidine and Ranitidine depending on their reaction with 1,4 Benzoquinone reagent at pH 5.2 and 5.6, respectively. The absorbances of the resulting condensation products were measured at 502 and 508 nm for Famotidine and Ranitidine, respectively. Concentrations adhering to Beers law were from 40-160 µg mL-1 for Famotidine and from 20-100 µg mL-1 for Ranitidine. Furthermore the resulting condensation products exhibited fluorescence at 665 nm when excited at 290 nm and the calibration graphs were rectilinear from 0.4-1.4 µg mL-1 for Famotidine and from 0.21 µg mL-1 for Ranitidine. Different parameters affecting these reactions were thoroughly studied. Also these methods were applied to the pharmaceutical preparations and the results were satisfactory. The validities of the methods were ascertained by the standard addition technique revealing fine results in consideration to the mean recovery percent and standard deviation. The spectrofluorimetric method was a hundred times more sensitive then the spectrophotometric method. The proposed methods were sensitive, accurate, and precise as statistically compared with the official methods of analysis of Famotidine and Ranitidine.
Spectrophotometry Fluorescence Standard additions calibration Standard method Optimization

"Spectrophotometric Determination Of Cefadroxil In Drug Formulations Using Flow Injection Analysis"
Anal. Lett. 1999 Volume 32, Issue 15 Pages 2977-2988
I. F. Al-Momani; I. Awni; H. S. Khalil; F. Esmadi

Abstract: A flow injection analysis method for the determination of cefadroxil is proposed. The method is based on the hydrolysis of cefadroxil in sodium hydroxide solution followed by treatment with 1,4-phenylenediamine and Fe(III) in sulfuric acid solution to produce a violet color which has a maximum absorption at 600 nn. Variables such as acidity, reagent concentrations, flowrate of reagents and other Fl parameters were optimized to produce the most sensitive and reproducible results. The calibration graph is linear between 80 -320 mg/l. The detection limit is 40 mg/l with a relative standard deviation, RSD (n=6) of 1.8%. The proposed method, combining the advantages of speed and accuracy was applied to the determination of cefadroxil in pharmaceutical preparations. The results have been compared with those obtained using HPLC method (USP-procedure). Excellent agreement between the results of the proposed method and the HPLC method was observed.
Cefadroxil Spectrophotometry Optimization Method comparison

"Determination Of Bismuth In Pharmaceutical Products Using Liquid-liquid Extraction In A Flow Injection System"
Anal. Chim. Acta 2000 Volume 408, Issue 1-2 Pages 129-133
A. Alonso, M. J. Almendral, M. D. Báez, M. J. Porras, F. López Lavín and C. García de María

Abstract: A flow injection procedure for the determination of bismuth in pharmaceutical products is described. The procedure is based on the formation of an ion-pair between tetraphenylarsonium and the tetraiodobismuthate(III) anion. This ion-pair is extracted with chloroform and the absorbance of the organic phase is measured at 363 or 505 nm. The detection Limit (3 x baseline s.d.) is 1.5 x 10^-6 M (35 ng). The proposed procedure has a relative standard deviation of 1.6% (3.0 x 10^-5 M, n = 12), a linear application range between 2.3 x 10^-6 and 1.5 x 10^-4 M and a sampling frequency of 40 h-1. Under the proposed working conditions, only Pd(II), Pt(IV) and Au(III) interfere.
Bismuth Spectrophotometry Ion pair extraction

"Flow Injection Analysis Of Meloxicam Using UV-detection"
Pharmazie 2001 Volume 56, Issue 2 Pages 186-187
Sener, E.; Altiokka, G.; Atkosar, Z.; Tuncel, M.

Abstract: A method for the direct determination of meloxicam by flow injection analysis without colorizing the solutions and its application to the pharmaceutical preparations The optimum concentration. of MeOH, in view of peak morphol., was 10% to 50%. The best flow rate was 1 mL/min. Significant differences were observed in peak areas due to the low solubility of meloxicam below pH 7.
Meloxicam Spectrophotometry Optimization

"Non-spectrophotometric Methods For The Determination Of Vitamin C"
Anal. Chim. Acta 2000 Volume 417, Issue 1 Pages 1-14
S. P. Arya, M. Mahajan and P. Jain

Abstract: In view of the widespread use of Vitamin C, a large number of methods have been developed for quantifying Vitamin C contents in natural and fortified food samples and pharmaceuticals. It is therefore essential to assess these methods. Accordingly, this paper reviews non-spectrophotometric methods. 277 references.
Ascorbic acid Fluorescence LC Polarography Titrations Review

"Determination Of Ranitidine And Salbutamol By Flow Injection Analysis With Chemiluminescence Detection"
Anal. Chim. Acta 1999 Volume 384, Issue 2 Pages 151-158
Neil W. Barnett, Benjamin J. Hindson and Simon W. Lewis

Abstract: Flow injection analysis methodology is reported for the determination of ranitidine and salbutamol tin pharmaceutical formulations) based on their chemiluminescent reactions with tris(2,2-bipyridyl)ruthenium(III) and acidic potassium permanganate, respectively. While the log-log calibration function for ranitidine showed significant non linearity, the precision (measured as relative standard deviation) was 1.7% (n = 6 1 x 10^-5 IM) and the detection limit (3s blank) was 6 x 10^-7 M. A linear log-log calibration function was obtained for salbutamol, the precision being 2.7% (n = 6; 1 x 10^-7 M) with a detection limit (signal to noise ratio = 3) of 2.5 x 10^-8 M.
Ranitidine Salbutamol Chemiluminescence

"Flow Injection Biamperometric Determination Of Chloramphenicol And Related Nitro Compounds By On-line Chemical Photodegradation"
Anal. Chim. Acta 2000 Volume 404, Issue 1 Pages 141-150
J. A. García Bautista, J. V. García Mateo and J. Martínez Calatayud

Abstract: An unsegmented continuous-flow assembly for the determination of chloramphenicol is proposed. The determination is based on the on-line photodegradation of the drug in an NH4+/NH3 buffer at pH 10.4 by using a photoreactor consisting of a 697 cm long x 0.8 mm ID piece of PTFE tubing coiled around an 8 W low-pressure mercury lamp. Photodegraded chloramphenicol is detected by photolytic cleavage of nitrite from the:parent compound as well as by organic oxidizing photofragments, and their subsequent reaction with iodide ion, which is monitored biamperometrically. Triiodide thus formed is detected in excess iodide solution by polarizing two platinum electrodes at 100 mV. The calibration graph is linear up to 8 mg L-1 chloramphenicol; the Limit of detection is 0.05 mg L-1, the relative standard deviation is 0.4% (for 25 replicates of 10 mg L-1 drug) and the throughput 68 samples h-1. The proposed method was used to determine chloramphenicol in commercially available pharmaceutical formulations and human urine.
Chloramphenicol Biamperometry Electrode Clinical analysis UV reactor Optimization

"Flow Injection Biamperometric Determination Of Chloramine-T In Environmental, Pharmaceutical And Veterinary Samples"
Anal. Chim. Acta 2000 Volume 407, Issue 1-2 Pages 187-192
M. Catalá Icardo, D. Giménez Romero, J. V. García Mateo and J. Martínez Calatayud

Abstract: A flow injection assembly for the determination of chloramine-T is proposed. The sample (213 µl) is inserted into the carrier, de-ionized water flowing at 4.1 mi min-1. This carrier merges with a mixture of potassium iodide and sulphuric acid, and the resulting solution flows to the flow cell through a reactor 66 cm long. The chloramine-T oxidises the iodide to tri-iodide. The resulting iodide/iodine ratio is biamperometrically tested. The calibration graph is linear up to 65 µg mL-1 chloramine-T; the limit of detection is 0.5 µg ml-1; the relative standard deviation (r.s.d) of the calibration slope is 2.8% for a series of eight independent calibrations. The RSD of a series of 74 peaks for 40 µg mL-1 chloramine-T) is 0.8%, and the sample throughput 220 h-1. Few foreign substances interfered. The method is applied to pharmaceutical, veterinary and waste water samples.
Chloramine T Biamperometry Clinical analysis Interferences Preconcentration

"Indirect Determination Of Paracetamol In Pharmaceutical Formulations By Inhibition Of The System Luminol-H2O2-Fe(CN)(6)(3-) Chemiluminescence"
J. Pharm. Biomed. Anal. 1999 Volume 21, Issue 2 Pages 311-317
A. Gregorio Alapont, L. Lahuerta Zamora and J. Martínez Calatayud

Abstract: After a large drug scanning, the system Luminol-H2O2-Fe(CN)(6)(3-) is proposed for first time for the indirect determination of paracetamol. The method is based on the oxidation of paracetamol by hexacyanoferrate (III) and the subsequent inhibitory effect on the reaction between luminol and hydrogen peroxide. The procedure resulted in a linear calibration graph over the range 2.5-12.5 µg mL-1 of paracetamol with a sample throughput of 87 samples h-1. The influence of foreign compounds was studied and, the method was applied to determination of the drug in three different pharmaceutical formulations.
Acetaminophen Chemiluminescence Interferences Indirect

"Potentiometric Flow Injection Determination Of Vitamin C And Glutathione With A Chemically Prepared Tubular Silver Electrode"
Pharmazie 2000 Volume 55, Issue 12 Pages 913-916
Kolar, M., Dobcnik, D.; Radic, N.J.

Abstract: This paper describes the preparation and use of a tubular electrode by means of chemical pretreatment of a silver tube with mercuric (II) chloride solution and iodide solution in flow injection analysis (FIA). The electrode was used as a potentiometric sensor for the indirect determination of vitamin C and glutathione in a carrier stream containing iodine. A simple FIA system that consists of a peristaltic pump, an injection T valve, a tubular silver electrode and a saturated calomel reference electrode (SCE) was used. Some typical FIA parameters such as flow rate, tube length, sample volume and composition of the carrier stream were varied. After optimization of these parameters, the electrode was further characterized by a constant linear response within the concentration range for the vitamin C between 5 x 10^-5 and 5 x 10^-3 M at the slope of 60.5±1.0 mV/p (vitamin C). Glutathione has a linear concentration range between 5 x 10^-5 and 10^-2 M at a slope of 55.2±1.0 mV/p (glutathione). The experimental slope was in good agreement with the theoretical values. Some pharmaceutical products containing vitamin C were also tested. These results can be compared to the results obtained by the standard volumetric method for the determination of vitamin C and are also in good agreement with values declared by pharmaceutical manufacturers.
Ascorbic acid Glutathione Electrode Potentiometry Indirect Optimization Method comparison

"Flow Injection Analysis Of Pharmaceuticals"
J. Anal. Chem. 2001 Volume 56, Issue 4 Pages 313-323
M. I. Evgen'ev, S. Yu. Garmonov, L. Sh. Shakirova

Abstract: The current state and outlooks of the development of the fow-injection analysis of medicinal substances in pharmaceuticals and biological fluids are considered. The role of chemical, photochemical and enzymatic reactions of derivatization in the flow injection determination of pharmaceuticals is outlined. The role of detection methods in improving the selectivity and sensitivity of the flow injection analysis of pharmaceuticals and expanding its possibilities in pharmaceutical analysis is considered.
Drugs Chemiluminescence Amperometry Fluorescence Stopped-flow Immobilized enzyme Extraction Review

"Determination Of Metformin In Pharmaceutical Preparations Using Potentiometry, Spectrofluorimetry And UV-visible Spectrophotometry"
Anal. Chim. Acta 1999 Volume 378, Issue 1-3 Pages 299-311
Saad S. M. Hassan, Wagiha H. Mahmoud, Mohamed A. F. Elmosallamy and Abdel Hammeed M. Othman

Abstract: New, simple and convenient potentiometric, spectrofluorimetric and spectrophotometric methods are described for the determination of metformin in pharmaceutical preparations. The potentiometric technique is based on preparation of PVC membrane sensors incorporating metformin-reineckate, and metformin-tungstosilicate ion-pairs as electroactive species with dioctylphthalate and o-nitrophenyloctylether as plasticizers, respectively. A membrane consisting of carboxylated PVC plasticized with dibutylsebacate is also prepared and tested. These sensors give rapid Nernstian response for 10^-1 - 10^-5 M metformin at pH range 5-11. The metformin-tungstosilicate based sensor is used in a flow-through sandwich cell for flow injection potentiometric determination of metformin. Graphite sensors coated or doped with metformin-tungstosilicate-PVC, Cu-diethyldithiocarbamate and Ni-diethyldithiocarbamate are also prepared and used for monitoring the titration of the drug with tetraphenyl berate (TPB-), Cu2+ and Ni2+ ions, respectively. The spectrofluorimetric method depends on the reaction of metformin with chrysenequinone in alkaline medium to give a Schiffs base, which upon hydrolysis gives the free base. The latter in the presence of l-naphthol gives a fluorescent product with excitation and emission maxima at 450 and 520 nm, respectively. The fluorescence-concentration relationship is linear over the range 20-200 µg mL-1 metformin. The proposed spectrophotometric technique involves reaction of metformin with Cu2+ in basic medium to form a Cu-metformin complex. The complex is dissolved in cyclohexylamine and its maximum absorption at 540 nm is measured. Beers law is obeyed over the range 0.5-2 mg mL-1 metformin. Various cations, some nitrogenous compounds or drug excipients cause no interferences. Results obtained by these techniques are comparable and compare favorably with data obtained using the British Pharmacopoeia method.
Metformin Potentiometry Electrode Fluorescence Spectrophotometry Interferences Standard method Method comparison

"Flow Electrochemical Determination Of Ascorbic Acid In Real Samples Using A Glassy Carbon Electrode Modified With A Cellulose Acetate Film Bearing 2,6-dichlorophenolindophenol"
Anal. Chim. Acta 2000 Volume 409, Issue 1-2 Pages 113-121
Ageliki B. Florou, Mamas I. Prodromidis, Miltiades I. Karayannis and Stella M. Tzouwara-Karayanni

Abstract: An ascorbate sensor based on a glassy carbon electrode modified with a cellulose acetate polymeric film bearing 2,6-dichlorophenolindophenol (CA/DCPI-CME) was constructed. The overall reaction obeys a catalytic regeneration mechanism (EC mechanism) and the electrochemical rate constant kf for the electrocatalytic oxidation of ascorbic acid was evaluated. The modified electrodes were mounted in a flow injection (FI) manifold, poised at +100 mV versus Ag/AgCl/3 M KCl at pH 6.5 and utilized for the determination of ascorbic acid in beverages and pharmaceuticals. Good correlation with a reference method was attained. Interferents of various molecular sizes were tested. Calibration graphs were linear over the range 0.02-1 and 0.1-6 mM ascorbic acid for CA/DCPI sensors hydrolyzed in KOH and ZnCl2 solution, respectively. The throughput was 25 samples per hour and the CV was for a 0.4 mM ascorbic acid solution 0.75 (n=14) and 1.2% (n=10) for CA/DCPI sensors hydrolyzed in KOH and ZnCl2 solution, respectively. The recovery was 92-110%. The sensors showed very good repeatability and operational stability.
Ascorbic acid Electrode Electrode Method comparison Interferences

"Application Of Two- And Three-way Chemometric Methods In The Study Of Acetylsalicylic Acid And Ascorbic Acid Mixtures Using Ultraviolet Spectrophotometry"
Anal. Chim. Acta 2000 Volume 409, Issue 1-2 Pages 159-170
Marcelo M. Sena, Julio Cesar B. Fernandes, Laércio RoverJr., Ronei J. Poppi and Lauro T. Kubota

Abstract: In this work, mixtures of acetylsalicylic acid (ASA) and ascorbic acid (AA) were studied by ultraviolet spectrophotometry (210-300 nm) using parallel factor analysis (PARAFAC) and partial least square (PLS). The study was carried out in the pH range from 1.0 to 5.5 and with a concentration range from 1.0 x 10^-5 to 1.0 x 10^-4 mol L-1 of both analytes. PARAFAC was used for spectra deconvolution, pK(a) estimation for both acids and to check the presence of salicylic acid (SA), due to the possible ASA decomposition. The estimated first pK(a) was equal to 3.41 and 4.10 for ASA and AA, respectively. Multivariate calibration models using PLS at different pH and N-way PLS were elaborated for simultaneous determination of ASA and AA in pharmaceutical samples. The best models for the system were obtained with N-way PLS2 and PLS2 at pH 1.1. The results obtained for simultaneous determination of ASA and AA in samples were in agreement to the values specified by the manufacturers and the recovery was between 97.6 and 103.6%. Nevertheless, these models failed to predict ASA decomposition to SA in simulated samples. Thus, a new PLS-pH1 model considering SA was built and applied successfully in simulated samples.
Acetylsalicylic acid Ascorbic acid Spectrophotometry Chemometrics Simultaneous analysis Principal component analysis Deconvolution

"Analytical Pervaporation: An Advantageous Alternative To Headspace And Purge-and-trap Techniques"
Chromatographia 2000 Volume 52, Issue 5-6 Pages 265-272
M. D. Luque de Castro and L. Gámiz-Gracia

Abstract: An overview of the principles and general applications of analytical pervaporation is presented. The different designs of both the analytical pervaporation module and the continuous manifolds to which the pervaporator is connected are discussed. The versatility of this non-chromatographic continuous separation technique for circumventing some of the shortcomings encountered in the automation of the overall analytical process is shown. Examples of methods developed for samples (both liquid and solid) in the environmental, food and beverage, and clinical and pharmaceutical fields are shown. The potential of pervaporation as an alternative to static and dynamic well-established approaches such as headspace and purge-and-trap sampling prior to gas-chromatographic separation is demonstrated. Examples of this approach involving both solid and liquid samples are discussed.
Spectrophotometry Review Pervaporation

"A Flow-through Solid Phase UV Spectrophotometric Biparameter Sensor For The Sequential Determination Of Ascorbic Acid And Paracetamol"
Anal. Chim. Acta 2000 Volume 404, Issue 1 Pages 131-139
A. Ruiz-Medina, M. L. Fernández-de Córdova, M. J. Ayora-Cañada, M. I. Pascual-Reguera and A. Molina-Díaz

Abstract: For the first time, a continuous flow system with solid phase UV spectrophotometric detection (an optosensor) is described for the sequential determination of two analytes based on the alternate use of two carrier/self-eluting agents. The selective and sequential sorption of both on an active solid support (an anion exchanger gel placed in the detection zone into an appropriate quartz flow cell) is performed and their respective UV intrinsic absorbances monitored. Each carrier itself elutes the respective analyte from the solid support, so regenerating the sensing zone. Ascorbic acid and paracetamol in concentrations ranging from 0.3 to 20 µg mL-1 and from 0.4 to 25 µg mL-1, respectively, could be determined with this UV flow-through optosensor using sodium acetate/acetic acid (pH 5.6) and 0.05 M NaCl (pH 12.5), respectively as carrier/self-eluting solutions and Sephadex QAE A-25 anion exchanger gel as solid phase placed in the inner of an 1 mm optical path length quartz flow cell. The RSDs % (n = 10) were lower than 1.3 (for ascorbic acid) and than 1.5 (for paracetamol). Detection limits (criterion 3s) as low as 0.02 µg mL-1 were achieved in both cases. Application to the analysis of pharmaceutical samples (in addition to synthetic ones) testifies the utility of this sequential sensor, which tolerates amounts of the species usually accompanying the analytes much higher than those ones found in these samples.
Ascorbic acid Acetaminophen Spectrophotometry Dual detection Detector Solid phase detection Resin Sephadex

"Simultaneous Kinetic Spectrophotometric Determination Of Acetaminophen And Phenobarbital By Artificial Neural Networks And Partial Least Squares"
Anal. Chim. Acta 2000 Volume 419, Issue 2 Pages 185-196
Yongnian Ni, Chao Liu and Serge Kokot

Abstract: A kinetic spectrophotometric method has been developed for simultaneous quantitative determination of acetaminophen and phenobarbital in pharmaceutical preparations, and relies on the different kinetic rates of the analytes in their oxidative coupling reaction with 3-methylbenzothiazolin-2-one hydrazone (MBTH) in the presence of hydrochloric acid and the Fe(III) oxidant. The absorbance was measured and recorded from 440 to 740 nm every 60 s from 15 to 435 s. An artificial neural network (ANN) coupled with principal component analysis (principal component artificial neural network, PC-ANN) has been described, and its principles and applications were illustrated by a simulated kinetic system. The performance of the PC-ANN was compared with a conventional ANN model. PC-ANN, as well as ANN and partial least squares (PLS), were applied to a validation set of overlapping spectra containing kinetic data of binary mixtures with different concentration ratios of acetaminophen and phenobarbital. The results show that PC-ANN is the most efficient of the three chemometrics methods applied for prediction of the two analytes.
Acetaminophen Phenobarbitone Spectrophotometry Kinetic Neural network Partial least squares Multivariate calibration Stopped-flow Kalman filter

"Continuous Monitoring Of Amino Acids And Related Compounds With Poly(3-methylthiophene)-coated Cylindrical Carbon Fiber Microelectrodes"
Anal. Chim. Acta 1999 Volume 401, Issue 1-2 Pages 145-154
L. Agüí, A. González-Cortés, P. Yáñez-Sedeño and J. M. Pingarrón

Abstract: The use of cylindrical carbon fiber microelectrodes (CFMEs) modified with poly(3-methylthiophene) (P3MT) films as amperometric microsensors for continuous monitoring of some amino acids such as tyrosine (Tyr), tryptophan (Trp), L-dopa, and related compounds such as tyramine and ascorbic acid, as well as small peptides such as Trp-Ala and Tyr-Gly, is discussed. Important practical advantages with respect to conventional glassy carbon (GC) electrodes, and also with respect to P3MT-coated GC electrodes of conventional size are demonstrated. The electrocatalytic ability of the modified surface allows the possibility of applying moderate potentials for the amperometric detection of the above mentioned compounds. Flow injection experiments carried out using a phosphate buffer solution of pH 7.0 as the carrier, and an applied potential of +0.8 V showed that no cleaning or regeneration pretreatment was needed when working with the same polymer modified electrode during the whole working day. The effect of the presence of acetonitrile or methanol in the flowing solution was evaluated. A flow injection method with amperometric detection was developed for the determination of L-dopa in pharmaceutical preparations. Finally, the modified microelectrodes have also shown suitable for amperometric detection in liquid chromatography (LC). A mobile phase composed of 5 : 95 (v/v) methanol : phosphate buffer solution of pH 7.0 allowed a good separation of mixtures of ascorbic acid, L-dopa, Tyr, tyramine and Trp, with detection limits of around 160 pmol. Furthermore, the-possibility of detection of Tyr-and Trp-containing oligopeptides Was also demonstrated.
Amino Acids l-Dopa Electrode Electrode Buffer pH

"Flow Injection Solid-phase Spectrophotometry For The Determination Of Zinc In Pharmaceutical Preparations"
Anal. Chim. Acta 1999 Volume 383, Issue 3 Pages 309-315
Leonardo S. G. Teixeira, Fábio R. P. Rocha, Mauro Korn, Boaventura F. Reis, Sérgio L. C. Ferreira and Antonio C. S. Costa

Abstract: A flow system exploiting solid-phase spectrophotometry is proposed for the determination of zinc in pharmaceutical preparations. The chromogenic reagent 1-(2-tiazolylazo)-2-naphthol (TAN) was immobilized on C-18 bonded silica loaded into a homemade flow cell with 1 mm optical path and 78 mm(2) cross section. The flow cell was designed in such a way that the sensitivity is enhanced and the attenuation of the radiation beam due to scattering and absorption by the solid material is minimized. The flow cell was placed in the spectrophotometer so that the radiation beam was focused on the overall surface containing the adsorbing material. Reagent immobilization was performed online and allowed to work for at least one month. Analyte reaction, retention and detection were performed simultaneously, followed by elution with hydrochloric acid, The apparent molar absorptivity was estimated as 2.02 x 10(5) 1 mol-1 cm-1 and the procedure allowed the determination of zinc in the 0.04-4.0 mg L-1 range with a coefficient of variation of 3.3% (n=10). A sample throughput of 45 determinations per hour and a detection limit of 10 µg L-1 (99.7% confidence level) were achieved. The results agreed at a 95% confidence level with those found by inductively coupled plasma atomic emission spectrometry.
Zinc Spectrophotometry Solid phase detection C18 Method comparison Immobilized reagent

"A Protocol For High-throughput Drug Mixture Quantitation: Fast LC-MS Or Flow Injection Analysis-MS?"
LC-GC 2001 Volume 19, Issue 1 Pages 60-72
Kate Yu and Michael Balogh

Abstract: The authors compare fast LC-MS with a flow injection analysis-MS method for effective quantitation in the high-throughput environment of today's drug discovery laboratories.
Drugs Mass spectrometry Review High throughput

"The Investigation Of Chemiluminescence Reaction Characteristic Of The In Situ Electrogenerated Br-2 And Its Analytical Application For Isoniazid"
Acta Chim. Sin. 2001 Volume 59, Issue 6 Pages 945-949
ZHENG Xing-Wang,YANG Mei,ZHANG Zhu-Jun

Abstract: By both designing a novel electrolytic flow cell and using the flow - injection technique, the nascent Br-2 was in situ. electrogenerated on the surface of platinum electrode with constant current electrolytic method in the H2SO4 - KBr medium. It was then found that compared with reagent Br-2 as well as on - line electrogenerated Br-2, the in situ electrogenerated Br-2 could oxidize the isoniazid injected accompanying by a stronger chemiluminescence signal. Based on this observation, a new now - injection electrogenerated chemiluminescence method for the determination of isoniazid was proposed. At the same time, a new concept, which can be used to explore the CL properties of the in situ electrogenerated reagent and to improve the sensitivity of CL analysis, was also proposed.
Isoniazid Chemiluminescence Electrochemical reagent generation

"Sequential-injection Procedure For Determination Of Iodide In Pharmaceutical And Drinking Water Samples By Catalytic Reaction With Spectrophotometric Detection"
J. AOAC Int. 2001 Volume 84, Issue 2 Pages 337-341
José Antonio Erustes, Rafel Forteza, and Victor Cerdà

Abstract: A novel sequential-injection system was developed for determination of iodide at very low concentrations by using a kinetic method. The method is based on the catalytic effect of iodide on the redox reaction between Ce4+ and As3+ first described by Sandell and Kolthoff. The calibration curve is constructed by measuring the decrease of Ce4+ absorbance versus iodide concentration with a delay time of 30 s. The detection limit is 1.5 µg/L, the working temperature is 45°C, and the working range is 0.002-0.5 mg/L. Reasonable agreement was obtained when the method was applied to pharmaceutical and drinking water samples. The method has a sample throughput of approximately 15/h. [Journal Article; In English; United States]
Iodide Spectrophotometry Kinetic Method comparison Heated reaction

"Extraction Based On The Flow Injection Principle. 1. Description Of The Extraction System"
Anal. Chim. Acta 1978 Volume 98, Issue 1 Pages 1-7
Bo Karlberg and Sidsel Thelander

Abstract: An extraction system was developed, essentially consisting of a pump, a rotary valve, and a spectrophotmeter. The sample, 12-25 µL was introduced via the rotary valve into an aqueous stream (flow injection). The aqueous stream, containing the sample plug, was divided into small segments by an organic phase and led into a Teflon coil so that a regular pattern of the 2 phases was obtained. No air bubbles should be present. Separation of the 2 phases was achieved in a specially constructed fitting and the absorbance of the organic phase was measured. The construction and performance of the system are illustrated by determination of caffeine. Up to 100 samples/h can be analyzed with a relative precision of better than 1%
Caffeic acid Caffeine Spectrophotometry Sample preparation Apparatus Solvent extraction Phase separator Organic phase detection Preconcentration

"A Detailed Study Of Sample Injection Into Flowing Streams With Potentiometric Detection"
Anal. Chim. Acta 1978 Volume 98, Issue 2 Pages 193-203
Zs. Fehér and G. NagyK. Tóth and E. Pungor

Abstract: A new method developed by combining manual or coulometric injection into flowing streams and potentiometric detection is described. The potential-time curves obtained in a flow-through detector as a result of single injections are handled theoretically and examined practically. The effects of experimental parameters, concentrations and flow rates on the signal are discussed. A systematic survey of the potential use of the technique in analysis is given. Species can be determined easily either in the flowing stream or in the injected sample. Some applications in pharmaceutical and other types of analysis are listed, and the main advantages of the technique are summarized.
Bromine Chlorine Cyanide Thiocyanide Indium Enzyme, cholinesterase Uric acid Enzyme, urease Glucose Enzyme, glucose oxidase Urea Nitrogen, urea Potentiometry Coulometric injection

"Flow Injection Determination Of Meptazinol With Electrochemical Detection"
Anal. Chim. Acta 1979 Volume 111, Issue 1 Pages 281-285
H. K. Chan, A. G. Fogg

Abstract: A flow injection analysis system incorporating a glassy carbon voltammetric detector cell is described. Meptazinol (I) [54340-58-8] (0.01-10 µg mL-1) can be determined by electrochemical oxidation in a carrier stream of 0.05 M AcONa-0.1 M AcOH in 98% EtOH at sampling rates up to 80 samples per h.
Meptazinol Electrode Potentiometry Voltammetry Organic solvent

"Extraction Based On The Flow Injection Principle. 3. Fluorimetric Determination Of Vitamin B1(Thiamine) By The Thiochrome Method"
Anal. Chim. Acta 1980 Volume 114, Issue 1 Pages 129-136
B. O. Karlberg and Sidsel Thelander

Abstract: The thiochrome method for determination of vitamin B1 in pharmaceutical preparations has been adapted to a continuous flow system based on the flow-injection principle. The sample volume required for an analysis is about 150 /sml. For routine purposes a concentration range of 3 x 10^-4-6 x 10^-4 mg mL-1 is used. Results obtained with the system agree well with results obtained manually. The consumption of organic phase is 2-3 ml/sample and the sampling rate is 30/h. A sampling rate of 70/h is easily attained if necessary. The relative standard deviation is about 1%.
Vitamin B1 Thiamine Fluorescence Sample preparation Extraction

"Photochemical-reaction Detectors In Continuous-flow Systems: Applications To Pharmaceuticals"
Anal. Chim. Acta 1980 Volume 114, Issue 1 Pages 137-146
A. H. M. T. Scholten, U. A. Th. Brinkman and R. W. Frei

Abstract: Several basic parameters of a photochemical reactor coupled to a high-performance liquid Chromatographie system are discussed. The non-fluorescent clobazam and desmethylclobazam and three phenothiazines, which exhibit native fluorescence, are used as model compounds. On irradiation with ultra-violet light, the reaction products formed display fluorescence (clobazam, desmethylclobazam) or unproved fluorescence characteristics (phenothiazines). The effects of carrier stream (mobile-phase) composition, time of irradiation and band broadening in the reactor on the fluorescence signal are described. The polarity of the organic solvents used (methanol, ethanol, acetonitrile) appears to have an important effect on the fluorescence intensity. For clobazam and desmethylclobazam, detection limits of 70 and 120 pg, respectively, were calculated after an irradiation time of 28 s with methanol-0.01 M (pH 5) acetate buffer (1:1) as mobile phase. The method is applied to the determination of both compounds in serum and urine samples.
Clobazam Desmethylclobazam Phenothiazines Chromatography Fluorescence Photochemistry

"Use Of Solvent Segmentation In Continuous-flow Systems, And Fluorescence Labelling By Derivatization"
Anal. Chim. Acta 1980 Volume 114, Issue 1 Pages 147-154
C. E. Werkhoven-Goewie, U. A. Th. Brinkman and R. W. Frei

Abstract: Solvent segmentation is valuable for reactions with up to 23 min residence times. Dansylation of pharmaceutically important secondary and primary amines is used as a model system. Plugs of organic solvent minimize band broadening, and act as reagent carrier as well as product carrier. Continuous-flow dansylation provides a sensitive fluorimetric detection system suitable for AutoAnalyzer systems and HPLC.
Clovoxamine β-histine Fluorescence Sample preparation Solvent extraction

"Rapid Determination Of Corticosteroids In Pharmaceuticals By Flow Injection Analysis"
Anal. Chim. Acta 1980 Volume 114, Issue 1 Pages 155-163
John B. Landis

Abstract: The proposed method is based on the reduction of blue tetrazolium by the steroid in an alkaline medium to form a highly colored formazan. The effects of reagent concentration, temperature, flow rate, and manifold design on the reaction are discussed for a typical steroid, methylprednisolone acetate. Analytical readout is obtained within 30 s after sample introduction and up to 100 samples/h can be processed with baseline resolution between peaks. Typical relative standard deviations of 0.5% are obtained with 10 µL injection volumes. Results obtained by flow injection analysis are similar to those obtained with the AutoAnalyzer technique.
Corticosteroids Spectrophotometry

"Minimization Of Interference Effects From Iodine-consuming Samples In The Determination Of Water With The Karl Fischer Reagent In A Flow Injection System"
Anal. Chim. Acta 1981 Volume 132, Issue 1 Pages 215-218
Ingrid Kågevall, Ove Åström and Anders Cedergren

Abstract: A principal feature of the flow-injection approach for determination of water with the Karl Fischer reagent is the small influence of side reactions. This is confirmed by the determination of water in an iodine-consuming sample, penicillin (fugacillin).
Water Karl Fischer analysis Spectrophotometry Interferences Titrations

"Polarographic Determination Of Penicilloic Acid In Penicillin Preparations With A Flow Injection System"
Anal. Chim. Acta 1982 Volume 139, Issue 1 Pages 133-142
Ulf Forsman and Anders Karlsson

Abstract: A flow-injection method for the determination of the penicilloic acid content of benzylpenicillin, phenoxymethylpenicillin, ampicillin, cloxacillin and carbenicillin is described. The penicilloate is detected polarographically at a dropping mercury flow-through detector mounted on a conventional polarographic capillary. A constant potential of + 0.04 V vs. SCE is applied and the current is measured in the sampled direct current mode. A pH 9.2 borate buffer containing 0.05% Triton X-100 is used. Triton displaces the reduction wave of oxygen about 400 mV towards negative potentials so that deaeration is not necessary. The penicilloate gives linear calibration graphs for 2 x 10^-6-1 x 10^-4 M solutions. The relative standard deviation for 10 injections of a 5 x 10^-5 M solution is 0.2%. Results for the determination of penicilloate in the presence of large amounts of penicillin (the latter in 10^-1000-fold excess) are compared with results obtained by two titrimetric procedures.
Penicilloic acid Electrode Electrode Polarography

"Automatic Potentiometric Two-phase Titration In Pharmaceutical Analysis. 1. The Influence Of Ionic Surfactants On Some Protolytic Equilibria In The Aqueous Phase"
Anal. Chim. Acta 1982 Volume 140, Issue 1 Pages 77-88
Per-Arne Johansson, Gun Hoffmann and Ulf Stefansson

Abstract: The autoprotolysis constant of water is shown to be unaffected by the presence of 0.05 M hexadecylpyridinium chloride (HPC) and an organic phase (dichloromethane). In the presence of 0.05 M sodium dodecyl sulphate (SDS), however, the pH scale is shortened by about 0.2 units because of the formation and solubilization of dodecyl sulphuric acid. Constants for the distribution of some amines (lidocaine, prilocaine and tocainide) between an aqueous phase and a micellar phase of HPC are reported, as is the equilibrium constant for the extraction of the lidocaine/dodecyl sulphate ion pair into a micellar phase of SDS.
Anions Potentiometry Equilibrium constants Titrations

"A Polarographic And Spectrophotometric Routine Analyzer For Assaying Content Uniformity In Pharmaceutical Quality Control"
Anal. Chim. Acta 1983 Volume 145, Issue 1 Pages 41-50
Zsófia Fehér, György Horvai, Géza Nagy, Zsuzsanna Niegreisz, Klára Tóth and Ernö Pungor

Abstract: A serial analyzer with polarographic and spectrophotometric detection has been designed to speed up content uniformity tests in pharmaceutical quality control laboratories. The advantages of flow and discrete analysis are combined to provide the required speed and precision. Pharmaceutical preparations of diazepam, nitrazepam, spironolactone and pyridinolcarbamate have been tested satisfactorily. The system is easily constructed from commercially available hardware and a few home-made units. The problem of sample deaeration before polarographic measurements in flow systems is solved succesfully in a very simple way.
Diazepam Nitrazepam Spironolactone Pyridinolcarbamate Polarography Spectrophotometry

"A Microprocessor-controlled Flow Injection Analyser For The Determination Of Terbutaline Sulfate"
Anal. Chim. Acta 1983 Volume 145, Issue 1 Pages 219-223
Mats Strandberg and Sidsel Thelander

Abstract: The determination is based on the reaction with 4-aminoantipyrine and potassium hexacyanoferrate(III). The system is automatic with a microcomputer controlling the sampler and injection valve, reading the output from the spectrophotometer and evaluating the result. The system is intended for drug analysis, and the matrix viscosity can vary considerably between different formulations without affecting peak area measurements.
Terbutaline sulfate Drugs Spectrophotometry Computer

"Determination Of Sulfur(II) Compounds By Flow Injection Analysis With Application Of The Iodine/azide Reaction"
Anal. Chim. Acta 1985 Volume 173, Issue 1 Pages 343-348
Jan Kurzawa

Abstract: A 10 µL portion of the sample solution was injected into a carrier stream (1.4 mL min-1) of iodine - KI solution in 2% NaN3 solution (pH 5.9) in a simple flow injection apparatus that consisted essentially of a straight tube with a g.c. septum at one end, a side-arm for entry of the carrier solution near this end, and two platinum electrodes (p.d. 25 mV) near the other end for the amperometric detection. For rectilinear response within the ranges 20 to 100, 5 to 50, 1 to 11 and 0.1 to 1 ng µL-1 of S2O32-, concentration. of iodine in the carrier stream of 5 mM, 1 mM, 0.2 mM and 50 µM are recommended. The standard deviations (n = 7) for 50, 20, 5 and 0.3 ng µL-1 of S2O32- were 0.9, 0.7, 0.3 and 0.04 ng µL-1, respectively. Other compounds could be determined under the same conditions as for S2O32-: 2-mercaptopyrimidine, thiouracil, 2-thiobarbituric acid and 6-mercaptopurine at 0.1 ng µL-1 and S2-, cysteine, gluthathione and thiourea at 0.2 ng µL-1. Interference by species (e.g., SO32-) that reduce iodine but do not induce the iodine - N3- reaction could be assessed by omitting the NaN3 from the carrier solution, but for a >100-fold excess of the reductant separate calibration was required.
Sulfur compounds Sulfite Cysteine Glutathione Thiourea Thiouracil 2-thiobarbituric acid 6-Mercaptopurine Amperometry Electrode Interferences Catalysis

"Flow Injection Spectrophotometric Determination Of Enalapril In Pharmaceuticals With Bromothymol Blue"
Anal. Chim. Acta 1985 Volume 175, Issue 1 Pages 339-344
Toshhiro Kato

Abstract: Sample solution (20 µL) containing 1.5 to 60 µg mL-1 of enalapril(I), prepared by H3PO4 (pH 3) extraction of tablets, was introduced into a continuous aqueous stream (HCl - Na acetate buffer, pH 3.2, 1.0 mL min-1) and was extracted as its yellow ion pair with bromothymol blue into CH2Cl2 (fed at 0.75 mL min-1) in a 60-cm x 1.0-mm extraction coil. After segmentation and phase separation with use of a PTFE membrane (1.2 µm pore size) the absorbance of the ion pair was measured at 405 nm. The extraction efficiency was 93%. The graph of peak height vs. I concentration. was rectilinear for 1.5 to 60 µg mL-1. Up to 80 samples h-1 could be processed, with coefficient of variation of 3.4%, 1.1% and 0.98% (n = 10) for 1.5, 7.5 and 60 µg mL-1 of I, respectively. Determined concentration. of I in tablets agreed well with those obtained by HPLC. The I degradation products, and common excipients, did not interfere.
Enalapril Spectrophotometry Sample preparation Interferences Extraction Phase separator Teflon membrane

"Batch And Flow Injection Determination Of Ethylenediamine In Pharmaceutical Preparations"
Anal. Chim. Acta 1986 Volume 179, Issue 1 Pages 289-297
M. Milla, R. M. de Castro, M. Garcia-Vargas and J. A. Muñoz-Leyva

Abstract: The methods are based on the formation of an orange Cu(I) chelate of a Schiff base produced by the reaction of ethylenediamine(I) with pyridine-2-carboxaldehyde at pH 8.5 (borate buffer). The absorbance is measured after 10 min at 475 nm (e = 6210). In the batch method the response is rectilinear from 0.5 to 11.2 µg mL-1 of I, with a coefficient of variation of 0.61% (n = 11) at the 4.6 µg mL-1 level. With the flow injection system (55 samples h-1) the range is between 1.4 and 84.6 µg mL-1, with a coefficient of variation of 0.68% (n = 11) at the 36.2 µg mL-1 level. Tolerance levels for some ions in the presence and the absence of EDTA are listed. The methods were applied to the determination of I in aminophylline and pharmaceutical preparations.
Ethylenediamine Spectrophotometry Chelation Interferences

"Spectrophotometric Flow Injection Determination Of Ascorbic Acid By Generation Of Triiodide"
Anal. Chim. Acta 1986 Volume 184, Issue 1 Pages 243-250
J. Hernández-Méndez, A. Alonso Mateos, M. J. Almendral Parra and C. García De María

Abstract: Tri-iodide and its starch complex were generated in a flow injection system of three channels containing (a) 0.08 M KI plus 1.20 g L-1 of starch, (b) 46 µM-KIO3 in 1 mM H2SO4, and (c) carrier solution (pH 1.5 to 11.0), at flow rates of 1.5, 1.5 and 3.0 mL min-1, respectively; I3- and the starch complex were detected at 350 and 580 nm, respectively, and ascorbic acid(I) was measured as a negative peak. The range of rectilinearity depended on the concentration. of KIO3 and I was determined at concentration. of 0.1 to 40 µg L-1 with coefficient of variation of 1.5 to 8.0%. Results for different samples compared well with those obtained by titrimetry. The method has been applied to pharmaceutical preparations and fruit juice and jam containing vitamin C.
Ascorbic acid Spectrophotometry Method comparison

"Spectrophotometric Determination Of Chlorhexidine With Bromocresol Green By Flow Injection And Manual Methods"
Anal. Chim. Acta 1986 Volume 189, Issue 2 Pages 323-328
J. Martinez Calatayud and P. Campíns Falcó

Abstract: For the manual method, the sample solution containing chlorhexidine(I) is mixed with succinate buffer solution (pH ~5), 0.554 mM bromocresol green and 2.5% Triton X-100 solution After dilution and centrifugation of the solution, the absorbance of the supernatant solution is measured at 630 nm (e = 12,500); Beer's law is obeyed from 2.9 to 32.2 µg mL-1 of I and the coefficient of variation is 0.4 to 1.3%. In the flow injection method, the sample solution, containing 23.0 to 83.9 µg mL-1 of I, is injected into a stream (at 3.14 mL min-1) of 72.6 µM-bromocresol green containing succinate buffer (pH 5) and 0.06% of Triton X-100, and the absorbance is measured at 630 nm; Beer's law is obeyed for the cited concentration. range and the coefficient of variation is 0.8%. Tolerances for benzocaine, aspirin, ascorbic acid and sucrose are reported and the I - bromocresol green - Triton X-100 system is discussed.
Chlorhexidine Spectrophotometry Interferences Tecator Triton X Surfactant

"Flow Injection Determination Of Sugars With Immobilized Enzyme Reactors And Chemiluminescence Detection"
Anal. Chim. Acta 1988 Volume 205, Issue 1-2 Pages 195-205
Cathy A. (Koerner) Swindlehurst and Timothy A. Nieman

Abstract: In the determination of glucose, the sample (80 µL) was injected into a carrier stream of 1 mM phosphate buffer (pH 6.5), which was passed through a reactor (5.6 cm x 3 mm) containing glucose oxidase and aldose 1-epimerase, immobilized on controlled-pore glass, and the H2O2 produced was determined via its chemiluminescence reaction with luminol in the presence of peroxidase at pH 11.6. Sucrose, maltose, lactose and fructose were determined similarly after their enzymatic conversion into glucose (with β-fructofuranosidase and aldose 1-epimerase, glucan 1,4-α-glucosidase, β-galactosidase, and glucose isomerase, respectively). Calibration graphs were rectilinear from 0.2 µM to 1 mM glucose, -sucrose and -maltose (limit of detection 0.1 µM) and 3 µM to 1 mM lactose and -fructose (limit of detection 1 µM). Analysis time was ~2 min.
Sugars Sucrose Maltose Glucose Lactose Fructose Carbohydrates Chemiluminescence Controlled pore glass Immobilized enzyme

"A Flow Injection System Based On Immobilized Penicillinase And A Linear PH-buffer For Potentiometric Determination Of Penicillin"
Anal. Chim. Acta 1988 Volume 209, Issue 1-2 Pages 123-133
Bo Olsson

Abstract: Penicillins were determined in a flow injection system by hydrolysis of the β-lactam ring, with detection of the acid formed at a combined glass electrode. Samples were injected into a carrier stream (1 mL min-1) of a buffer the pH of which varied between pH 6 and 8, depending on the acid concentration, and the solution passed through an immobilized β-lactamase reactor. The difference in electrode response of the sample stream before and after passing through the enzyme reactor was related to the penicillin concentration. The calibration graph was rectilinear from 0.1 to 15 mM. The coefficient of variation were 0.5 and 1.0% for 10 and 1 mM penicillin, respectively. Mean recoveries from 10 mM I containing up to 10 mM HCl were 100.3% for peak area and 99.8% for peak height measurements.
Penicillins Electrode Potentiometry Gradient technique Immobilized enzyme

"Indirect Atomic Absorption Spectrometric Determination Of Local Anesthetics In Pharmaceutical Preparations With A Flow Injection Precipitation Technique"
Anal. Chim. Acta 1988 Volume 215, Issue 1-2 Pages 241-248
R. Montero, M. Gallego and M. Valcárcel

Abstract: The ppt. formed by injecting Co(II) into a sample stream containing 10 to 110 µM-lignocaine, -amethocaine or -procaine at pH 8.0 to 9.1 was retained on a stainless-steel filter and analyzed by online AAS at 240.7 nm. The amount of pptd. Co was proportional to the concentration. of local anaesthetic in the sample. Chemical variables such as sample pH, Co(II) concentration. and temperature together with flow injection variables were optimized to ensure manifold simplicity (diagram given), minimum sample pre-treatment, and max. response function. The detection limit was 1.2 µg mL-1, the coefficient of variation was 0.6% and the sampling frequency was 100 h-1.
Anaesthetics Lidocaine Amethocaine Procaine Tetracaine Spectrophotometry Indirect Optimization Precipitation

"Quantitation Of Sodium Hydrogen Sulfite In Parenteral Samples By A Flow Injection Method"
Anal. Chim. Acta 1989 Volume 220, Issue 1 Pages 281-285
Dennis R. Jenke

Abstract: Sodium hydrogen sulfite in pharmaceutical formulations (1 µL) was injected into a stream of 0.03% 3,3'-dithiobis-(6-nitrobenzoic acid) solution in 44 mM citric acid buffer of pH 6.0 (1 mL min-1) and, after passage through a 2.5 mL reaction coil, the absorbance was measured at 410 nm. The processing time was 4 min per injection. The calibration graph was rectilinear from 1 ng (practical detection limit) to 1 µg of NaHSO3 injected, and coefficient of variation were 1.5% at 10 mg L-1 and ~7% at 3 mg l-1. Matrix components did not interfere.
Hydrogen sulfite Spectrophotometry Buffer Interferences Detection limit

"Flow Injection Analysis Of Vitamin D3 And 25-hydroxyvitamin D3 By Amperometric Detection"
Anal. Chim. Acta 1989 Volume 225, Issue 1 Pages 247-251
A. Sanchez Perez, M. Delgado Zamarreño, J. Hernandez Mendez and R. M. Sanchez Rodriguez

Abstract: The determination of cholecalciferol (I) and 25-hydroxycholecalciferol (II) in pharmaceutical preparations is described. Sample solution in aqueous 70% methanol was injected into a carrier stream (1.4 mL min-1) of 75 mM LiClO4 in aqueous 60% methanol, and, after mixing in a 25-cm coil, I and II were determined with use of a vitreous-carbon electrode at +1.05 V vs. Ag - AgCl. Calibration graphs were rectilinear for 0.18 to 10 µm-I or II. Detection limits were 7 and 11 ng, respectively, and coefficient of variation were 1.5 and 1.6% (n = 10).
Vitamin D3 25-Hydroxyvitamin D3 Cholecalciferol 25-Hydroxycholecalciferol Amperometry Electrode

"Flow Injection Extraction-spectrophotometric Determination Of Bismuth As Tetraiodobismuthate(III) With The Tetramethylenebis(triphenylphosphonium) Cation"
Anal. Chim. Acta 1989 Volume 225, Issue 2 Pages 449-453
D. Thorburn Burns, N. Chimpalee and M. Harriott

Abstract: Bismuth was extracted into CH2Cl2 as tetramethylenebis(triphenylphosphonium) tetraiodobismuthate, after reaction with 2% of KI and 0.4% of tetramethylenebis(triphenylphosphonium) bromide in 2 M H2SO4; the product was determined at 495 nm. The calibration graph was rectilinear for 20 µg mL-1 of Bi, and the detection limit was 0.24 µg mL-1. The injection rate was 20 h-1, and the coefficient of variation was 0.6% for 10 µg mL-1 (n = 10). Interference by Na, Mg, Ca and Zn was negligible. This simple, rapid method was successfully applied to pharmaceutical samples.
Bismuth Spectrophotometry Sample preparation Interferences Extraction

"Quantitative Validation Of A Flow Injection Determination Of Penicillin In Pharmaceutical Formulations By Means Of A Validation Program Based On An Expert System"
Anal. Chim. Acta 1990 Volume 233, Issue 1 Pages 65-76
R. Wolters, M. A. J. van Opstal and G. Kateman

Abstract: A generally applicable validation program, VALID, based on an expert system program is described. The automated penicillin assay was performed by enzymatic hydrolysis of penicillin to penicilloic acid, which reacts with iodine generated online. The iodine consumption was measured by using an amperometric detector (cf., Kok et al., Ibid. 1984, 162, 19). During the program run, the system evaluated the calibration procedure, the drift of the analytical system and the effect of the sample matrix. The reliability of the flow injection method was estimated by evaluating the max. total error, which includes random and systematic errors. The latter was assessed by comparing the results with those obtained by titration with Hg(II). The user requirement for the assay was a max. total error of 10%. The validation procedure showed that the analytical method complied with the requirements for the major part of the concentration. range of 66 to 250 µM.
Penicillin Amperometry Computer Automation Titrations Expert system Indirect

"5,5-Diethylbarbiturate Tubular Electrode For Use In Flow Injection Detection Systems"
Anal. Chim. Acta 1990 Volume 234, Issue 1 Pages 221-225
José L. F. C. Lima and M. Conceição B. S. M. Montenegro, J. Alonso, J. Bartroli and J. G. Raurich

Abstract: A tubular electrode was prepared, sensitive to barbitone (I), based on tetraoctylammonium I in 2-nitrophenyl octyl ether as liquid ion-exchanger on PVC membranes. The characteristics of the electrode were examined and compared with those of a conventional electrode. The use of the electrode to determine I in pharmaceutical preparations was evaluated with use of a double-channel flow injection manifold. Results showed reasonable agreement with those of the official B.P. method. The detection limit was ~1 mM I, and response was rectilinear to ~0.3 mM I. The electrode was unaffected by pH in the range 9 to 11.5.
Barbitone Electrode Electrode Ion exchange Sensitivity Detection limit pH Standard method Method comparison

"Gas Diffusion Dilution Flow Injection Method For The Determination Of Ethanol In Beverages Without Sample Pretreatment"
Anal. Chim. Acta 1990 Volume 234, Issue 1 Pages 213-220
Wolfgang Künnecke and Rolf D. Schmid

Abstract: Sample was injected into water as carrier stream and passed to a gas diffusion unit, in which ethanol passed through a membrane into a stream of 0.1 M phosphate buffer (pH 7.5). This solution was passed through a column containing immobilized alcohol oxidase, and the H2O2 produced was detected at a platinum working electrode at 700 mV vs. Ag - AgCl. The limit of detection was 6 ppm or 0.1 mM ethanol (coefficient of variation 5.2%, n = 15 to 20), and up to 60% ethanol could be determined, depending on the membranes used. The coefficient of variation was generally 0.2 to 0.7%. Up to 180 samples h-1 could be analyzed. The operational half-life of the immobilized enzyme was 8000 injections in 44 h. The method was applied to beer, wine, spirits and pharmaceuticals.
Ethanol Electrode Gas diffusion Membrane Immobilized enzyme

"Determination Of Quinine And Quinidine By Continuous-flow Chemiluminescence"
Anal. Chim. Acta 1990 Volume 236, Issue 2 Pages 463-468
Ioanna I. Koukli and Antony C. Calokerinos

Abstract: A chemiluminescence analyzer. [Koukli et al., Analyst (London), 1988, 113, 603] with an air-segmented continuous-flow manifold (diagram given) was used to determine quinine and quinidine by their sensitizing action on the reaction between Ce(IV) and SO32-. The Ce(IV) solution in 0.1 M H2SO4 was segmented with air before introduction of the analyte solution also in 0.1 M H2SO4. The stream was de-bubbled, then mixed with the SO32- solution before entering the coil for generation of chemiluminescence. The calibration graph for either analyte (log-log scale for quinine) was rectilinear from 5 to 500 µg mL-1, and the analysis rate was 40 h-1. The limit of detection was 0.64 and 1.6 µg mL-1 for quinidine and quinine, respectively. The method was successfully applied to pharmaceuticals.
Quinine Quinidine Chemiluminescence Segmented flow Debubbler Detection limit Calibration Segmented flow

"Kinetic Determination Of Sulfonamides At The Millimolar Level By The Continuous Addition Of Reagent Technique"
Anal. Chim. Acta 1990 Volume 237, Issue 2 Pages 353-359
M. Márquez, M. Silva and D. Pérez-Bendito

Abstract: A sulfonamide solution was mixed with 5 mM 1-naphthol in ethanol and 1.0 M acetic acid - Na acetate buffer (pH 4.15) and the mixture was diluted with water. The reaction was developed by continuous addition of 1 M NaNO2 at 0.5 mL min-1 with stirring at 200 rpm. The production of an azo dye was monitored at 470 nm. The calibration graph was rectilinear from 3 to 30 µM. The coefficient of variation for 18.7 µM-sulfonamide was 1.0% (n = 11) and the sampling rate was 25 h-1. The detection limit was 1.5 to 2.0 µM. The method is more sensitive than a reported flow injection method and more rapid than the conventional photometric micellar method. The technique was used for the determination of sulfonamides in pharmaceuticals.
Sulfonamides Kinetic Buffer Dilution Calibration Detection limit Sensitivity

"Flow Injection Spectrophotometric Determination Of Arylamines And Sulfonamides By Diazotization And Coupling In A Micellar Medium"
Anal. Chim. Acta 1991 Volume 242, Issue 1 Pages 143-146
J. S. Esteve Romero and G. Ramis Ramos, R. Forteza Coll and V. Cerdá Martin

Abstract: In the flow injection system, sample solution (0.66 mL min-1) was mixed with aqueous 0.2% NaNO2 (0.17 mL min-1), and the mixture was passed through a 4-m coil and mixed with aqueous 1.5% sulfamic acid (0.17 mL min-1). After passage through a 4-m coil, a portion of the eluate was mixed with 0.01% N-(1-naphthyl)ethylenediammonium dichloride in aqueous 0.5% Na dodecyl sulfate (0.34 mL min-1), the mixture was passed through a 3-m coil, and the absorbance was measured at 550 nm. The flow rates were optimized. For aniline, ethyl 4-aminobenzoate, sulfanilamide, sulfamethizole and sulfathiazole, limits of detection were 0.11 to 0.5 µg mL-1, and coefficient of variation (n = 3) were 3.0% for 5 µg mL-1. Calibration graphs were rectilinear for up to, e.g., 11 µg mL-1. The method was applied to pharmaceutical preparations; results showed good agreement with declared values.
Amines, aromatic Sulfonamides Aniline ethyl-4-aminobenzoate Sulfanilamide Sulfamethizole Sulfathiazole Spectrophotometry Micelle Optimization

"Chemiluminescence Determination Of Vitamin B12 By A Flow Injection Method"
Anal. Chim. Acta 1991 Volume 243, Issue 1 Pages 127-130
Y. K. Zhou, H. Li, Y. Liu and G. Y. Liang

Abstract: In the cited method, the sample stream was mixed with a reagent stream containing 30 mM luminol and 40 mM H2O2 (total flow rate 7 mL min-1; optimum pH ~10.9) before passage through a cell for chemiluminescence measurement. The signal was unaffected by acidification of the sample solution with HCl. The calibration graph [constructed for Co(NO3)2] was rectilinear from 5 µg to 50 ng; the detection limit was 1.0 ng for 50 µL injections. The method was applied to the analysis of three vitamin preparations; coefficient of variation (n = 3) were 0.9 to 1.2%. Results agreed with those obtained by spectrophotometry.
Vitamin B12 Chemiluminescence Method comparison

"Photochemical Derivatization And Fluorimetric Determination Of Reserpine In A Flow Injection Assembly"
Anal. Chim. Acta 1991 Volume 245, Issue 1 Pages 101-108
J. Martinez Calatayud, C. Gomez Benito

Abstract: The fluorimetric flow injection determination of reserpine was achieved with the drug being derivatized online by photoreaction. PTFE tubing was helically coiled around a germicide lamp located between the injection valve and detector. Two analytical procedures are proposed using either dilute acetic acid or pure methanol as the carrier stream. The influence of foreign compound was studied and the method was applied to the determination of reserpine in pharmaceutical formulations. Reserpine solution (1.52 mL min-1) merged with 10 M acetic acid (2.58 mL min-1) and a portion (466 µL) was injected into the carrier stream of dilute acetic acid (2.99 mL min-1). The stream passed though a PTFE tube (260 cm) wound helically around a germicidal lamp (254 nm, 30 W), and the oxidation products were determined fluorimetrically (excitation at 382 nm, emmision at 486 nm). Alternatively, sample solution could be mixed with anhydrous acetic acid - methanol (3:2) and the carrier stream could be methanol (2.56 mL min-1). The calibration graphs were rectilinear over the ranges 0.02 to 2.0 and 2.0 to 120 mg L-1 and 0.005 to 1.0 and 1.0 to 120 mg L-1 for the aqueous and methanolic systems, respectively. Detection limits were 0.9 and 0.16 µg l-1, the coefficient of variation were 0.8 and 2.3% and the sample throughputs were 57 and 45 h-1 for the aqueous and methanolic systems, respectively. Pharmaceutical formulations were dissolved in 1 M acetic acid for analysis.
Reserpine Fluorescence Photochemistry UV reactor Interferences Helically coiled tube

"Comparison Of Two Fibre-optic L-glutamate Biosensors Based On The Detection Of Oxygen Or Carbon Dioxide, And Their Application In Combination With Flow Injection Analysis To The Determination Of Glutamate"
Anal. Chim. Acta 1991 Volume 248, Issue 2 Pages 351-359
Bernd A. A. Dremel and Rolf D. Schmid, Otto S. Wolfbeis

Abstract: Food or pharmaceutical prep. was dissolved in boiling H20 and the mixture was filtered. The filtrate was subjected to flow injection analysis with mixing with the carrier solution [0.1 M potassium phosphate buffer (pH 7.0 or 5.0)] and passing through an air damper before detection in the flow-through cell with use of a glutamate biosensor. The biosensor was based on (i) oxygen optrode with immobilized glutamate oxidase, or (ii) carbon dioxide optrode with immobilized glutamate decarboxylase. Detection was at 495 or 560 nm (excitation at 400 or 460 nm) for detectors (i) and (ii), respectively. The corresponding calibration graphs were rectilinear for 0.02 to 1 mM and 0.1 to 2.5 mM glutamate. The coefficient of variation were ~3% (n = 5). Interference from volatile acids was observed with detector (ii). Detector (i) was recommended.
Carbon dioxide Glutamate Oxygen Fluorescence Sensor Optrode Buffer Immobilized enzyme Interferences Optical fiber

"Simultaneous Determination Of Amitriptyline, Imipramine And Perphenazine In Pharmaceutical Preparations And Blood Serum By Multi-wavelength Spectrophotometry"
Anal. Chim. Acta 1991 Volume 252, Issue 1-2 Pages 107-113
J. M. García Fraga, A. I. Jiménez Abizanda, F. Jiménez Moreno and J. J. Arias León*

Abstract: Several methods were developed for the simultaneous determination of the binary mixtures amitriptyline-imipramine (1.00-10 µg mL-1), amitriptyline-perphenazine (1.00-30.00 and 1.00-8.00 µg mL-1) and imipramine-perphenazine (1.00-30.00 and 1.00-8.00 µg mL-1) and the ternary mixture amitriptyline-perphenazine-imipramine using a diode-array spectrophotometer and a multi-component analysis program. The methods were applied to the determination of the components of synthetic perphenazine-imipramine mixtures, real amitriptyline-imipramine and amitriptyline-imipramine-perphenazine mixtures in blood serum and real amitriptyline-perphenazine mixtures in pharmaceutical preparations.
Amitriptyline Imipramine Perphenazine Spectrophotometry Multivariate calibration

"Flow Injection Determination Of Zinc By Fluorescence Spectrometry"
Anal. Chim. Acta 1991 Volume 255, Issue 2 Pages 325-328
R. Compañó, S. Hernández-Cassou and M. D. Prat*, L. García-Beltrán

Abstract: A flow injection manifold is illustrated in which a stream of succinate buffer solution (pH 6.1) containing masking agents, 0.1 M Na2S2O3 and/or Na pyrophosphate, was merged with a stream of Brij-35 surfactant (both at 5 mL min-1) in a 60-cm coil, before mixing with the sample stream (58 µL). The mixture was reacted with 1 mM 5,7-dichloro-2-methylquinolin-8-ol in aqueous 40% ethanol (1 mL-1) in a 30-cm coil, before fluorimetric detection at 534 nm (excitation at 397 nm). The calibration graph was rectilinear from 10 to 600 µg L-1 of Zn, with a detection limit of 3 µg l-1. The coefficient of variation (n = 15) was 1.8% for 200 µg Zn. Tolerance limits for interfering ions are tabulated; sampling time was 180 h-1. The method was applied to potable water and pharmaceutical preparations and results were in good agreement with those obtained by AAS and the values stated by manufacturers, respectively. The masking agent was more efficient in this flow injection system than one in which the reagent stream was mixed with the buffer and surfactant streams before mixing with the sample stream.
Zinc Fluorescence Buffer Interferences Surfactant

"Flow Injection Extraction-spectrophotometric Determination Of Salbutamol By Oxidative Coupling With 4-amino-NN-dimethylaniline"
Anal. Chim. Acta 1992 Volume 260, Issue 1 Pages 65-68
D. Thorburn Burns*, N. Chimpalee, D. Chimpalee and K. Leiwongcharoen

Abstract: Aqueous sample solution was injected into a carrier stream (1 mL min-1) of water which merged sequentially with streams of aqueous 5% NaHCO3 solution (1 mL min-1), aqueous 0.1% 4-amino-NN-dimethylaniline sulfate solution (1 mL min-1), aqueous 0.5% potassium hexacyanoferrate(III) solution (1 mL min-1) and CHCl3 (0.8 mL min-1). The mixture was passed through a reaction coil (2 m x 0.8 mm), an extraction coil (5 m x 0.8 mm) and a phase separator before the absorbance of the organic extract was measured at 605 nm. The calibration graph was rectilinear for 20 µg mL-1 of salbutamol (I); the detection limit was 0.7 µg mL-1. For the determination of 10 µg mL-1 of I, the coefficient of variation (n = 10) was 1.9%. Results obtained in the analysis of two dosage forms agreed with the labelled contents. Salbutamol was determined spectrophotometrically at 605 nm after flow injection extraction into CHCl3 solution after oxidative coupling with 4-amino-N,N-dimethylaniline. The carrier stream was distilled water and the reagents streams contained 5% NaHCO3, 0.5% potassium hexacyanoferrate(III) and 0.1% 4-amino-N,N-dimethylanilinium sulfate. The sampling rate is 20 h-1. The calibration graph was linear up to 20.0 µg mL-1 salbutamol, based on injection volume 100 µL. The relative standard deviation was 1.9% for 10 µg mL-1 salbutamol. The system was applied to the determination of salbutamol in pharmaceutical formulations.
Salbutamol Spectrophotometry Sample preparation Organic phase detection Phase separator Solvent extraction

"Cerium(IV) Arsenite As A Solid-phase Reactor For Use In Flow Injection Analysis: Spectrophotometric Determination Of Promethazine"
Anal. Chim. Acta 1992 Volume 264, Issue 2 Pages 283-289
J. Martínez Calatayud* and V. Garcia Mateo

Abstract: Cerium(IV) arsenite is used as a strongly oxidizing solid-phase reactor in an unsegmented continuous-flow injection assembly. Its preparation procedure produces particles of uniform size with suitable physico-chemical properties for use in a continuous-flow system. A manifold is proposed for the determination of promethazine in pharmaceutical preparations by spectrophotometric monitoring of the red color produced by the oxidized drug. A linear calibration graph is obtained over the range 5-400 µg mL-1 of promethazine. A manifold is described for the determination of promethazine hydrochloride (I) in pharmaceuticals and involved oxidation by Ce(IV) with monitoring of the transient red color formed at 514 nm. The calibration graph was rectilinear from 5 to 400 µg mL-1 of I and the coefficient of variation was 0.5% (n = 40). Detection limits may be improved by fluorimetric detection and the method may be applied in the quality control of pharmaceutical preparations. Cerium(IV) arsenite is used as a strongly oxidizing solid-phase reactor in an unsegmented continuous-flow injection assembly. Its preparation procedure produces particles of uniform size with suitable physicochem. properties for use in a continuous-flow system. A manifold is proposed for the determination of promethazine in pharmaceutical preparations by spectrophotometric monitoring of the red color produced by the oxidized drug. A linear calibration graph was obtained over the range 5-400 µg mL-1 of promethazine. pharmaceuticals.
Promethazine hydrochloride Spectrophotometry Oxidation column Solid phase reagent

"Automation Of Enzymic Hydrolysis By Use Of Continuous-flow Methods Involving Immobilized Biocatalysts"
Anal. Chim. Acta 1992 Volume 264, Issue 2 Pages 275-282
J. M. Fernández-Romero, M. D. Luque de Castro and M. Valcárcel

Abstract: Two flow injection methods are described and applied to the hydrolysis of 4-nitrophenyl β-D-glucuronide catalyzed by β-D-glucuronidase. The products were monitored: aglycone (spectrophotometric method) and glucuronic acid (chemiluminescent method). Calibration graphs were rectilinear from 1 to 700 µM with a coefficient of variation of 1.5%, and 0.17 to 1.72 mM with a coefficient of variation of 1.4 to 8.1%, for the spectrophotometric and chemiluminescent methods, respectively. The methods may be applied in the determination of illegal drugs in anti-doping control, monitoring pharmaceuticals in therapeutic programmes and monitoring in industrial systems. Two flow injection methods for online enzymatic hydrolysis using immobilized biocatalysts are proposed and applied to the hydrolysis of 4-nitrophenyl-β-D-glucuronide catalyzed by β-D-glucuronidase. Monitoring is performed via the 2 hydrolysis products of glucuronides: the aglucone (specific spectrophotometric method) and glucuronic acid (universal chemiluminescence method). The spectrophotometric method afforded a linear determination range of 1-700 µM with excellent precision, RSD <1.5%, and a sampling frequency of 130 h-1. The chemiluminescence method provided a linear determination range of 0.05-5.5 mM, a RSD between 1.48 and 3.07% for concentrations of 0.17 and 1.72 mM, respectively, and a sample throughput of 25 h-1. The yield of the enzymatic process and the stability of the enzyme reactor were determined by using urine samples. Two fully automated approaches to online hydrolysis and collection and monitoring of the hydrolyzate are also proposed.
4-nitrophenyl β-D-glucuronide Chemiluminescence Spectrophotometry Automation Catalysis Linear dynamic range Process monitoring Immobilized enzyme

"Flow Injection Determination Of Sulfonamides With Fluorimetric Or Photochemical - Fluorimetric Detection"
Anal. Chim. Acta 1992 Volume 269, Issue 2 Pages 193-198
M. C. Mahedero, J. J. Aaron*

Abstract: A flow injection method incorporating photochemically induced fluorescence (PF) or native fluorescence (NF) for the determination of sulfonamides is described. The PF method was applied to the determination of sulfadimidine (I) and the NF method was applied to sulfanilamide (II), sulfaguanidine (III) and sulfacetamide (IV). The system (diagram given) consisted of an Ismatec IPN-4 peristaltic pump, a rotary injection valve, a 254 nm low pressure mercury lamp irradiating a PTFE reactor (0.5 mm i.d.) and a spectrofluorimeter with fluorescence detection at 350 nm (excitation at 284 nm) for I and at 345 nm (excitation at 260 nm) for II, III, and IV. Calibration graphs were rectilinear over one order of magnitude. Detection limits were between 15 to 120 ng mL-1 of the sulfonamides. The method was applied to the detection of sulfonamides in pharmaceuticals and milk. A flow injection method with photochem. induced fluorescence (PF) or native fluorescence (NF) detection was developed for the determination of four sulfonamides. Sulfamethazine was determined using PF and sulfanilamide, sulfaguanidine and sulfacetamide using NF. Linear calibration graphs were obtained over a concentration. range of one order of magnitude. The relative standard deviations were within the range 0.4-5%. Limits of detection were between 0.015 and 0.12 µg mL-1. The method was applied to the determination of sulfonamides in milk and pharmaceutical preparations.
Sulfanilamides Fluorescence Photochemistry

"Continuous-flow Chemiluminometric Determination Of Dihydralazine, Rifampicin And Rifamycin SV By Oxidation With N-bromosuccinimide"
Anal. Chim. Acta 1993 Volume 272, Issue 2 Pages 251-263
Stergios A. Halvatzis, Meropi M. Timotheou-Potamia* and Themistocles P. Hadjiioannou

Abstract: A continuous-flow method (diagram given) for the cited determinations, based on measurement of chemiluminescence produced during oxidation of the analytes by N-bromosuccinimide, is described. Sample solution were allowed to stand in alkaline solution for four hours before measurement in order to degrade chemiluminogenic products. Emission intensity was enhanced by the presence of ammonia. Solutions were analyzed at the rate of 105 h-1 with a relative error of 1 to 3%. Dihydralazine sulfate was determined in the range 2 to 30 µg mL-1 with a detection limit of 1.23 µg mL-1. Rifampicin was determined in the range 0.02 to 1 µg mL-1 with a detection limit of 0.0017 µg mL-1, and rifamycin was determined in the range 0.005 to 1 µg mL-1 with a detection limit of 0.0005 µg mL-1. The mean recoveries were 99.2%, 99.9% and 101.9% respectively. The method was applied to the analysis of pharmaceutical preparations.
Dihydralazine Rifampicin Rifamycin Chemiluminescence

"Flow Injection Analysis With Electrochemical Detection For Determination Of Salicylic Acid In Pharmaceutical Preparations"
Anal. Chim. Acta 1993 Volume 273, Issue 1-2 Pages 469-475
M. Neumayr, O. Friedrich and G. Sontag*, F. Pittner

Abstract: A solution of the sample in 3 mL of 20 mM phosphate buffer/1 mM EDTA of pH 7.6 (buffer A) was mixed with 163 µL of 12 mM β-NADH. A 20 µL portion of the solution was injected into a stream (1 ml/min) of buffer A, which was then passed through a Waters Guard Column 84550 (4 cm x 4 mm) containing salicylate 1-mono-oxygenase (I) immobilized on aminosilane-modified tetrachloro-p-benzoquinone-activated glass beads (3.5 mg of I per 100 mg of beads). The catechol produced by the I-catalyzed hydroxylation of salicylic acid (II) was determined amperometrically in an EA 1096 wall-jet cell (Metrohm) at a vitreous-carbon electrode at 0.45 V vs. Ag/AgCl/saturated KCl. The calibration graph was rectilinear for 5-150 µg/ml of II; the detection limit was 0.4 µg/ml. When the method was applied to pharmaceutical preparations, recoveries of 92.9-98.9% with respect to the stated contents and RSD of 0.5-2.0% (n = 3 to 6) were obtained. When stored at 4°C the immobilized I was stable for >1 year. Under assay conditions the activity of the beads decreased initially and then was constant for >1 year.
Salicylic acid Electrochemical analysis Electrode EDTA Catalysis Glass beads

"Determination Of Thiamine By In Situ Sensitized Photochemical Spectrofluorimetry"
Anal. Chim. Acta 1993 Volume 276, Issue 1 Pages 151-160
Xiang-Qun Guo*, Jin-Gou Xu, Yu-Zhou Wu, Yi-Bing Zhao, Xian-Zhi Huang and Guo-Zhen Chen

Abstract: The cited photochemical spectrofluorimetric flow injection method is based on the conversion of thiamine in alkaline medium into an intensively fluorescent compound. The photochemical reaction was sensitized by acetone. The fluorescence measurements were made with a spectrofluorimeter equipped with an 125-W Xe lamp, an 18 µL flow cell and a peristaltic pump (schematic diagram given). The solution was irradiated for 60 s at 280 nm and the fluoresence was measured at 440 nm (excitation at 370 nm). The calibration graph was rectilinear up to 10 µg mL-1 of thiamine and the detection limit was 0.46 ng mL-1; the coefficient of variation at 50 ng mL-1 was 1.5%. The method was applied to pharmaceuticals.
Vitamin B1 Thiamine Fluorescence Photochemistry UV reactor

"Determination Of Fluphenazine Hydrochloride In A Flow Assembly Incorporating Cerium(IV) Arsenite As A Solid-bed Reactor"
Anal. Chim. Acta 1993 Volume 276, Issue 2 Pages 281-286
S. Laredo Ortiz and C. G&oacute;mez Benito, J. Mart&iacute;nez Calatayud*

Abstract: The cerium(IV) arsenite was prepared as previously reported (Martinez Calatayud and Garcia Mateo, Ibid., 1992, 264, 283), and the bed-reactor was prepared by filling a PTFE tube (18 cm x 1.5 mm). This reactor was incorporated in a flow injection system with 10 mM H3PO4 as carrier solution and fluorimetric detection at 410 nm (excitation at 352 nm); the calibration graph was rectilinear from 0.05 to 100 ppm of fluphenazine hydrochloride. This method has been applied (after aqueous extraction) to pharmaceutical preparations, and data are presented concerning interference from other compounds in these preparations.
Fluphenazine hydrochloride Fluorescence Solid phase reagent Interferences

"Spectrofluorimetric Determination Of Emetine By Flow Injection Using Barium Peroxide And UV Derivatization"
Anal. Chim. Acta 1993 Volume 279, Issue 2 Pages 293-298
C. G&oacute;mez Benito and T. Garc&iacute;a Sancho, J. Mart&iacute;nez Calatayud*

Abstract: Emetine, an alkaloid in ipecacuanha, is an amoebicide acting principally in the bowel wall and in the liver. Sample stream (1 ml/min) was merged with a reagent stream (0.55 ml/min) containing 40 mg of barium peroxide in 4.0 M phosphoric acid. A portion of the mixture was injected into a water carrier stream (4.3 ml/min) and transported through a PTFE tube (2.65 m x 0.5 mm) coiled around a Hg lamp before fluorimetric detection at 452 nm (excitation at 350 nm). The calibration graph was linear for 0.05-50 µg/ml of emetine. The RSD (n = 34) for 3.5 µg/ml of emetine was 0.65% and the sample throughput was 67/h. The tolerance limits for foreign compounds found in pharmaceutical materials are listed. Resorcinol produces the most serious interference. The repetitive analysis of human urine and injection solution spiked with 4 µg/ml of emetine resulted in relative errors of 3.4 and 0.3%, respectively.
Emetine Fluorescence Spectrophotometry Photochemistry UV reactor Interferences

"Room Temperature Phosphorescence Optosensor For Tetracyclines"
Anal. Chim. Acta 1993 Volume 281, Issue 3 Pages 637-644
Fausto Alava-Moreno, Marta Elena D&iacute;az-Garc&iacute;a and Alfredo Sanz-Medel

Abstract: A flow-through optosensor for tetracyclines based on the tetracycline-europium chelate room temperature phosphorescence energy transfer is proposed. The sensor is developed in conjunction with a flow injection analysis system and is based on the transient immobilization on a non-ionic resin (packed in a flow-through cell) of the tetracycline-europium chelate. The analytical performance characteristics of the proposed sensor for semiautomated analysis and control of very low levels of tetracycline were as follows: the detection limits for tetracycline, oxytetracycline and chlortetracycline were 0.25, 0.30 and 0.40 ng mL-1, respectively, with a relative standard deviation of 1% for determination of 0.24 µg mL-1 of each antibiotic (n = 10). Most of the common metal ions in biological samples did not interfere, except Fe(III) which caused serious interference and should be masked with 1,10-phenanthroline. The recommended method has been successfully tested for determination of tetracyclines in clinical samples (urine and pharmaceutical preparations). [References: 18]
Tetracycline Oxytetracycline Chlorotetracycline Phosphorescence Sensor Optosensing Interferences

"Determination Of Promethazine By Its Inhibition Of The Chemiluminescence Of The Luminol-hydrogen Peroxide-chromium(III) System"
Anal. Chim. Acta 1993 Volume 282, Issue 1 Pages 169-174
Abdulrahman A. Alwarthan, Saad A. Al-Tamrah and Akel A. Akel

Abstract: The FIA manifold is illustrated. A portion of 0.1 M Cr(III) is injected by a solenoid-activated rotary valve into a carrier stream of 1 mM luminol in 0.1 M sodium carbonate buffer of pH 10.5, and this stream merges with a stream of 0.01 M H2O2 and then with the sample solution stream (all flow rates 2.1 ml/min). The merged streams pass into a flow cell and the chemiluminescence signal is recorded with a photomultiplier tube. The log.-log. calibration graph is linear up to 0.1 mM promethazine, and the detection limit is 3 nM. The RSD (n = 10) at 10 µM-promethazine was 1.3%. Results for two pharmaceutical products agreed with those obtained by the B.P. method.
Promethazine Chemiluminescence Method comparison Standard method

"Electrochemical Oxidation Of Lysergic Acid-type Ergot Alkaloids In Acetonitrile. 1"
Anal. Chim. Acta 1993 Volume 282, Issue 2 Pages 289-296
Tibor Dankh&aacute;zi, &Eacute;va Fekete, Krisztina Pa&aacute;l and George Farsang

Abstract: The ergot alkaloids are an important group of compounds used extensively in medicine. An intrinsic property of these molecules is that the ergoline compounds decompose spontaneously in an oxidative process. A systematic study was carried out with the aim of describing the stoichiometry of the electrochemical oxidation reaction which simulates the oxidative degradation. Eight ergo- and 9.10-dihydroergopeptides were investigated, including the group of 9,10-dihydroergotoxine alkaloids and simple ergoline derivatives. Cyclic voltammetry, controlled-potential coulometry and isolation and identification of the electrochemically oxidized forms led to the conclusion that the electrochemical oxidation of all lysergic acid-type ergot alkaloids takes place in the same way. The main oxidation product is always a highly conjugated dimer, and the dimerization is located at the indole part of the ergoloid skeleton. The study of the stoichiometry of the oxidative electrode reaction of lysergic acid-type ergot alkaloids is described, which provides a theoretical and experimental basis for the liquid chromatographic or flow-injection determination with amperometric detection of these alkaloids in different pharmaceutical formulations.
HPLC Electrochemical analysis

"Automated Flow Injection Serial Dynamic Dialysis Technique In The Study Of Drug Binding With Cyclodextrins"
Anal. Chim. Acta 1994 Volume 289, Issue 1 Pages 87-95
E. E. Siderisa, C. A. Georgioub, M. A. Koupparisb,* and P. E. Macherasa

Abstract: The dialysis unit consisted of two identical chambers (1 mL each) separated by a semi-permeable membrane (670 mm2) with 20 µm pores. A cyclodextrin (CD)/drug solution at 25±0.5°C was recirculated through the donor chamber of the unit at 9.6 ml/min. The acceptor chamber was connected to the carrier solution reservoir and the UV detector via two 3-way solenoid values which were controlled by a timing module. The carrier solution was the same as the buffer used in the donor chamber and the sampling time was 25 s. The procedure was used to study the binding of p-nitrophenol, salicylic acid and ibuprofen with α- or β-CD in various buffer solution A dialysis time was 3 min for p-nitrophenol and 2 min for salicylic acid and ibuprofen with detection wavelengths of 399 nm for p-nitrophenol, 237 nm for salicylic acid at pH 1.5 and 296 nm at pH 7.4 and 200 nm for ibuprofen. Calibration graphs were prepared for 0.1-1 mM p-nitrophenol and 0.1-3 mM salicylic acid and ibuprofen. The absorbance peaks were used to calculate the concentration of the unbound drug.
Phenols, nitro Salicylic acid Ibuprofen Spectrophotometry Dialysis

"Flow Injection Biamperometry Of Phenothiazine Derivatives"
Anal. Chim. Acta 1994 Volume 289, Issue 3 Pages 339-346
Jacek Michaowskia, Anatol Kojoa,*, Beata Magnuszewskaa and Marek Trojanowiczb

Abstract: A flow injection amperometric method for the determination of promazine and thioridazine was developed. Sample solution (450-500 µL) was injected into a carrier stream of water (3.3 ml/min) which was then merged with a reagent stream (2.8 ml/min) containing 0.18 M Fe(III) in 2 M HCl. The resulting stream was passed through a reaction coil (100 cm x 0.5 mm i.d.) at 60°C to the flow-through detector cell which contained two Pt electrodes at a potential difference of 150 mV. The calibration graphs were linear for 40-160 mg/l of promazine and 40-140 mg/l of thioridazine and the detection limits were 0.4 and 0.5 mg/l, respectively. The maximum sampling rate was 90 samples/h for both analytes. The method was applied to the analysis of four pharmaceutical preparations and the RSD (n = 12) were 0.8%. Results were confirmed by spectrophotometric analysis.
Promazine Thioridazine Amperometry Electrode Spectrophotometry

"Flow Injection Chemiluminometric Determination Of Steroids"
Anal. Chim. Acta 1994 Volume 290, Issue 1 Pages 190-200
Nikolaos T. Deftereos and Anthony C. Calokerinos*

Abstract: A fully automated flow injection method is described for the determination of 0.02-5 µg/ml of cortisone, 0.02-1 µg/ml of hydrocortisone and 0.2-5 µg/ml dexamethasone in aqueous solution and 1-20 µg/ml of prednisolone, methylprednisolone, progesterone, corticosterone and testosterone and 2-20 µg/ml betamethasone in 20% acetonitrile solution The chemiluminometric method was based on the sensitizing action of the steroids on the Ce(IV)-sulfite reaction. Sample (500 µL) was injected into a 1 mM Na2SO3 stream which was merged with a 1 mM cerium(IV) sulfate stream. A 300 µL portion of the mixture was passed through the coiled glass tube detector cell (90 x 2 mm i.d.) and the chemiluminescence was detected by a photomultiplier tube. The calibration graphs were linear for the ranges given above and the detection limits were 0.013-4 µg/ml. The RSD (n = 7) for up to 5 µg/ml of steroids were typically 1.5%. The mean recovery of steroids from pharmaceutical preparation was 102.6%. The proposed method was validated by analyzing commercial steroid formulations.
Steroids Chemiluminescence

"Continuous-flow Chemiluminometric Determination Of Amiloride And Streptomycin By Oxidation With N-bromosuccinimide"
Anal. Chim. Acta 1994 Volume 290, Issue 1 Pages 172-178
Stergios A. Halvatzis, Alexandros M. Mihalatos, Leonidas P. Palilis and Antony C. Calokerinos*

Abstract: Sample stream (11.8 ml/min) containing 0.5-15 µg/ml of amiloride (I) in 3 M NaOH or 2-30 µg/ml of streptomycin (II) in 1 mM NaOH was merged with a 0.02 M N-bromosuccinimde stream (5.33 or 11.8 ml/min for amiloride and streptomycin, respectively). The merged streams were passed through a coiled glass flow-through detector cell (90 x 2 mm i.d.; 300 µL) mounted in front of a photomultiplier tube and the chemiluminescence signal was recorded. Calibration graphs were linear for the ranges given above and the detection limits were 0.16 and 1.61 µg/ml for I and II, respectively. The RSD (n = 6) for 2-10 µg/ml of I and 5-10 µg/ml of II were 0.4-3.4%. The sampling frequency was 250 samples/h. The method was applied to commercial pharmaceutical preparations. The mean recoveries of 3-5 µg/ml of I and 5-10 µg/ml of II from spiked solution prepared from various pharmaceutical preparations were 95.3 and 102.2%, respectively.
Amiloride Streptomycin Chemiluminescence

"Flow Injection Determination Of Kanamycin By Inhibition Of The Lucigenin-hydrogen Peroxide-cobalt(II) System"
Anal. Chim. Acta 1994 Volume 292, Issue 1 Pages 201-208
Abdulrahman A. Alwarthan*, Saad A. Al-Tamrah and Akel A. Akel

Abstract: The method is based on the inhibiting effect of kanamycin on the Co(II)-catalyzed chemiluminescent reaction between lucigenin and H2O2 in alkaline medium. A portion of 1 mM Co(II) solution was injected into a 1 mM lucigenin carrier stream (3.5 ml/min) and this was mixed in turn with streams of 10 mM H2O2, 0.1 M KOH and analyte solution (all flows at 3.5 ml/min) before entering a flow-through cell where the chemiluminescence was measured as described previously (cf., Ibid., 1993, 282, 169). The detection limit was 0.1 pM-kanamycin and the calibration graph was linear for up to 10 µM-kanamycin. At the 0.6 µM level the RSD was 1.91% (n = 10). The method was relatively free from interferences from common excipients used in pharmaceutical preparations of the analyte. Results for four pharmaceutical preparation agreed with those obtained by a spectrophotometric procedure (cf., Rizk and Younis, Anal. Lett., 1984, 17, 1803).
Kanamycin Chemiluminescence Spectrophotometry Interferences

"Evaluation Of PH Field Effect Transistor Measurement Signals By Neural Networks"
Anal. Chim. Acta 1994 Volume 294, Issue 3 Pages 243-249
Bernd Hitzmann* and Thomas Kullick

Abstract: A feed-forward neural network was developed which allowed both the analyte concentration and the buffer concentration to be calculated from a FIA signal of a pH-FET detector. The method was applied to the determination of penicillin G (benzylpenicillin) using a detector prepared by immobilizing penicillin amidase on to the gate area of the pH-FET. The detector was mounted in a FIA system which employed phosphate buffer solution, pH 7, as the mobile phase. The detector responded to both the presence of penicillin and buffer ion producing changes in peak height and contour. The neural network was used to evaluate the different contours of the signal. The net was trained with all combinations of 1.5, 5 and 10 g/l benzylpenicillin with 5, 20, 35 and 50 mM buffer ion and with all combinations of 2.5 and 7.5 g/l benzylpenicillin with 15, 25 and 45 mM buffer ion. The total average errors were 4.7 and 4.9% for benzylpenicillin and phosphate buffer ion, respectively.
Benzylpenicillin Field effect transistor Ion exchange Neural network

"Determination Of Reserpine By In Situ Sensitized Photochemical Spectrofluorimetry"
Anal. Chim. Acta 1995 Volume 302, Issue 2-3 Pages 207-214
Jin-Gou Xu*, Hui-Ping Chen, Xiang-Qun Guo and Yi-Bing Zhao

Abstract: An in situ photochemical spectrofluorimetic method for the rapid and precise determination of reserpine was proposed. Adding acetone to the reserpine solution in acetic acid medium will speed up the photochemical conversion of reserpine into an intensively fluorescent compound. The determination can be carried out by measuring the fluorescence intensity at a fixed time. The mechanism of the sensitization of acetone was also discussed. The linear concentration range of the calibration graphs was found to be 0-0.91 µg mL-1. The detection limit was 0.40 ng mL-1 reserpine and the relative standard deviation was 0.75% for 0.40 ng mL-1 reserpine (n = 6). The recovery for its application to reserpine injections was 97.3-103%. Through a standard addition recovery test, we obtained a recovery between 91.3 and 100% in urine samples. Interference effects of some common ions in serum and foreign substances coexisting with reserpine in complex reserpine tablets were also tested.
Reserpine Fluorescence Photochemistry

"Individual And Joint Stopped-flow Kinetic Spectrofluorimetric Determination Of Neomycin And Tyrothricin"
Anal. Chim. Acta 1995 Volume 303, Issue 1 Pages 31-37
B. Gala, A. G&oacute;mez-Hens and D. P&eacute;rez-Bendito*

Abstract: Kinetic methodology was used for the first time to develop a simple, fast spectrofluorimetric method for the determination of neomycin and tyrothricin using the stopped-flow mixing technique. The proposed method involves reaction of these antimicrobial substances with o-phthaldialdehyde in the presence of n-acetylcysteine, which is used as a thiol reagent. Neomycin and tyrothricin can thus be determined simultaneously by applying the proportional-equation method to the initial rate and signal increment of the kinetic curves obtained for each analyte. The reaction rate can be determined in ~1 s and the signal increment in ~3 s. The calibration graph was linear over the range 0.07-70 µg mL-1 neomycin and 0.08-40 µg mL-1 tyrothricin. The mid-range relative standard deviation was less than 3%. The proposed method was applied to the individual determination of these compounds in pharmaceutical samples, with a recovery of 98.1-103.6% for neomycin and 92.0-108.0% for tyrothricin. Synthetic mixtures of neomycin and tyrothricin in ratios between 1:4 and 4:1 were also satisfactorily analyzed.
Drugs Neomycin B Tyrothricin Fluorescence Kinetic Stopped-flow

"Enzymic Sensor Coupled To A Flow Injection Analysis System For The Determination Of Salicylate"
Anal. Chim. Acta 1995 Volume 305, Issue 1-3 Pages 26-31
M. Neumayr*, G. Sontag and F. Pittner

Abstract: The enzymatic sensor for salicylate was prepared by covalently immobilizing salicylate hydroxylase to a Pt electrode (5 mm diameter) via p-tetrachloroquinone and crosslinking with glutardialdehyde. The sensor was used at +0.55 V vs. Ag/AgCl/KClsat. in a flow injection system with 1 mM EDTA in 20 mM phosphate buffer at pH 7.5 as the carrier solution (0.5 ml/min). A 40 µL volume of 60 mM β-NADH solution was added to 1 mL of each sample or standard solution prior to the injection of 20 µL portions. The calibration graph for salicylate was linear for up to 4.35 mM and the detection limit was 7.25 µM. The RSD (n = 10) for 360 µM-salicylate was 2%. The sensor was applied to the determination of salicylate in pharmaceuticals following dilution with carrier solution. The sample throughput was 60 samples/h and the sensor was stable for at least 3 months.
Salicylate Sensor Electrode Electrode

"Flow Injection Spectrophotometric Determination Of Carbimazole And Methimazole"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 457-461
C. S&aacute;nchez-Pedre&ntilde;o*, M. I. Albero, M. S. Garc&iacute;a and V. R&oacute;denas

Abstract: A flow injection method for the determination of carbimazole (I) and methimazole (II) was based on the formation of yellow complexes between these antithyroid drugs and Pd(II). A 72 µL portion of antithyroid solution was injected into a water carrier stream (1.5 ml/min) which was merged with a reagent stream (1.5 ml/min) containing 0.25 mM PdCl2 in 0.5 M HCl. After passing through the reaction coil (2 m x 0.5 mm i.d.), the absorbance of the flow was measured at 325 nm for both analytes. The calibration graphs for both I and II were linear for 0.01-0.5 mM and the detection limits were 3.5 µM-I and 3 µM-II. The RSD for the determination of 0.1 mM I or II were ±0.7 or ±0.35%, respectively. The method was applied to the analysis of pharmaceutical preparations. The method was also applicable to the determination of II in human urine following therapeutic administration of the drug.
Carbimazole Methimazole Spectrophotometry

"Continuous-flow-spectrophotometric Determination Of Sulfadiazine By Diazotization With In Situ Preparation Of Nitrite"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 451-456
A. Mellado Romeroa, C. G&oacute;mez Benitoa and J. Mart&iacute;nez Calatayudb,*

Abstract: An FIA method was developed for the determination of sulfadiazine using a solid-phase reactor of copperized Cd for the preparation of the nitrite reagent. The nitrite reagent stream was generated by passing a solution containing 10 mM KNO3 in NH3/EDTA buffer through the solid-phase reactor at 2.3 ml/min. The resulting stream was merged with a sample stream (2.3 ml/min) in 0.1 M HCl. A 642 µL volume of this mixture was injected into a water carrier stream (4.8 ml/min) which was merged with a 3.9 mM N-(1-naphthyl)ethylendiamine dihydrochloride stream (2.7 ml/min). The absorbance at 542 nm was measured using a diode-array spectrophotometer equipped with a 18 µL flow cell (1 cm path length). The calibration graph for sulfadiazine was linear for 0.5-50 µg/ml and the detection limit was 0.5 µg/ml. The method was applied to the analysis of pharmaceutical preparations.
Sulfadiazine Spectrophotometry Solid phase reagent

"Precipitation Flow Injection Method For The Determination Of Saccharin In Mixtures Of Sweeteners"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 275-280
M. C. Yebra, M. Gallego and M. Valc&aacute;rcel*

Abstract: An indirect method for the determination of saccharin in the presence of other sweeteners was developed based on the precipitation of silver saccharinate from an acetic acid medium. A solution containing 5-75 µg/ml saccharin in 5% acetic acid and a 100 µg/ml of AgNO3 solution at pH 1.9 were pumped continuously for 30s at 1.2 and 0.4 ml/min, respectively, and mixed in a precipitation coil. The precipitate was collected on a screen type stainless-steel filter (3 cm2 filtration area, 0.5 µm pore size) and washed with 5% acetic acid at 3.5 ml/min for 1 min. The precipitate was dissolved in a 1 M NH3 stream (3.5 ml/min) and aspirated into an AAS flame. Ag was determined at 328.1 nm with an air/acetylene flame. The calibration graph was linear for 5-75 µg/ml saccharin, the detection limit was 3 µg/ml and the RSD (n = 11) for 30 µg/ml saccharin was 2.7%. The sampling frequency was 20 samples/h. The method was not applicable to chlorine-containing samples. The method was applied to the determination of saccharin in commercially available mixtures of solid sweeteners for addition to drinks and pharmaceutical preparation. The results were consistent with manufacturers` specifications.
Saccharin Spectrophotometry Precipitation Indirect Filter

"Spectrofluorimetric Determination Of Berberine In Oriental Pharmaceutical Preparation By Flow Injection Analysis Coupled With Liquid-liquid Extraction"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 329-333
Tadao Sakai*, Noriko Ohno, Yong Soon Chung and Harumitu Nishikawa

Abstract: Ground pharmaceutical preparations were extracted with hot water and the cooled extracts were analyzed. A 120 µL portion of the prepared solution was injected into a buffered 1 mM sodium perchlorate stream (1.24 ml/min) of pH 5.5. The stream was merged with a 1,2-dichloroethane stream (0.62 ml/min) and passed through an extraction coil (0.5 m in length). The phases were separated using a double membrane phase separator and the fluorescence of the organic phase was measured at 516.8 nm (excitation at 355.2 nm). The calibration graph for berberine was linear for 4 nM to 1 µM, the detection limit was 0.8nN and the RSD (n = 10) for the determination of 50 nM-berberine was 0.5%. The sampling frequency was 42 samples/h.
Berberine Drugs Fluorescence Sample preparation Sample preparation Extraction Phase separator Organic phase detection

"Flow Injection Chemiluminometric Determination Of Ascorbic Acid Based On Its Sensitized Photo-oxidation"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 299-307
Tom&aacute;s P&eacute;rez-Ru&iacute;z*, Carmen Mart&iacute;nez-Lozano and Antonio Sanz

Abstract: The chemiluminescent reaction between lucigenin and the photo-oxidation products of ascorbic acid was utilized for the determination of ascorbic acid. The FIA system allowed 275 µL sample solution and 215 µL 1 mM toluidine blue (as photosensitizer) to be injected simultaneously into two phosphate buffer streams (both at 1.1 ml/min) at pH 3. The streams were merged before passing through a photoreactor equipped with a reaction coil (2 m x 0.5 mm i.d.) and a W halogen lamp. The stream was merged with streams of 0.1 mM lucigenin (1.1 ml/min) and 0.7 M KOH (4.1 ml/min). The three merged zones travelled 6 cm (0.5 mm i.d.) to the detector cell were the chemiluminescence was measured with a photomultiplier tube. The calibration graph was linear for 1.1 nM-0.3 mM ascorbic acid and the detection limit was 0.2 nM. The RSD (n = 11) for the determination of 0.2 mM, 20 µM and 0.7 µM-ascorbic acid were 0.43, 1.65 and 1.22%, respectively. The sampling frequency was 80 samples/h. The method can be applied to the determination of ascorbic acid in pharmaceutical preparations, fruit juices, soft drinks and blood serum.
Ascorbic acid Chemiluminescence Photochemistry

"Spectrofluorimetric Flow Injection Determination Of Adrenaline With An Iodine Solid-phase Reactor"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 334-338
A. Kojlo* and J. Mart&iacute;nez Calatayud

Abstract: The determination of adrenaline was based on its oxidation to adrenochrome which, in turn, was converted to a fluorescent substance, adrenolutine, by alkali. The solid phase reactor was prepared by impregnating the flexible PVC tubing (1.02 mm i.d.) of the pump with iodine. The flow injection manifold allowed 452 µL of sample solution to be injected into a water carrier stream (1.04 ml/min). After passing through the pump, the flow was merged with a reagent stream (0.43 ml/min) containing 1.25 M NaOH and 0.3 µM-ascorbic acid. The flow passed to the detector where the fluorescence was measured at 510 nm (excitation at 330 nm). The calibration graph for adrenaline was linear for 5-25 mg/l and the detection limit was 1 mg/l. The RSD (n = 10 or 15) for the determination of 10 and 20 mg/l adrenaline were 1.8 and 2.6%, respectively. The sampling frequency was 30 samples/h. The method was applied to the analysis of pharmaceutical preparations.
Adrenaline Fluorescence Solid phase reagent PVC membrane

"Flow Injection Stopped-flow Spectrofluorimetric Kinetic Determination Of Total Ascorbic Acid Based On An Enzyme-linked Coupled Reaction"
Anal. Chim. Acta 1995 Volume 309, Issue 1-3 Pages 271-275
Houping Huang,*, Ruxiu Cai, Yumin Du and Yune Zeng

Abstract: Wine, beer or urine were adjusted to pH 6 with HCl or NaOH and 0.1 M EDTA added. Solid dose formulations of ascorbic acid were dissolved in 100 mL 1% oxalic acid and liquid formulations of ascorbic acid were diluted with water. To 1 mL portions containing ~0.5 µg/ml of ascorbic acid were added 5 µL aqueous 2 mg/ml of laccase and the solution injected in parallel with 10 mL 20 µM-o-phenylenediamine in 250 µM-phosphate buffer of pH 6 into a carrier stream (2 ml/min) of water and mixed in a 5 cm reaction coil at 35°C, and fluorimetric detection at 430 nm (excitation at 360 nm). Calibration graphs were linear for 0.025-1 µg/ml of ascorbic acid. Quantitative recoveries of ascorbic acid in the presence of Fe(III), Cu(II) and a range of common biochemical substrates were obtained, excepting L-cystine, L-cysteine, tyrosine and NH3OHCl.
Ascorbic acid, total Fluorescence Heated reaction Interferences Kinetic Stopped-flow

"Evaluation Of Multicomponent Flow Injection Analysis Data By Use Of A Partial Least Squares Calibration Method"
Anal. Chim. Acta 1995 Volume 310, Issue 1 Pages 53-61
O. Hern&aacute;ndez, A. I. Jim&eacute;nez, F. Jim&eacute;nez* and J. J. Arias

Abstract: A 132 µL sample of 0.454-1.59 µg/ml Co(II), 0.536-1.879 µg/ml Cu(II) or 0.322-1.612 µg/ml Zn(II) as nitrates was injected into a water carrier stream which was mixed sequentially with 0.5 M borate buffer of pH 9 and 0.1 mM 2-carboxy-2-hydroxy-5-sulfoformazylbenzene (Zincon). Formation of Co-Zincon (λmax = 656 nm, ε = 13 200), Cu-Zincon (λmax = 600 nm, ε = 27 300) and Zn-Zincon (λmax = 618 nm, ε = 50 600) complexes was completed in a reactor coil (160 cm x 0.5 mm i.d.) and spectra were recorded with a diode array spectrometer using an 18 µL flow cell. The overlapping spectra were resolved by multivariate calibration (details given). The RSD for Co, Cu and Zn were 0.018-0.048%, 0.02-0.052% and 0.004-0.011%, respectively. Up to a 100-fold excess of K, Li, Ba, Ca and Mg did not interfere; Mn and Ni did not interfere in 5-fold excess. Fe(III) was tolerated up to a 10:1 metal/interferent ratio in the presence of 0.1 M phosphate or 0.1 M NaF. Levels of Zn determined in blood serum were in good agreement with values determined by AAS; agreement for Cu was less satisfactory. The levels of Co, Cu and Zn found in veterinary products agreed with those determined by AAS.
Cobalt Copper Zinc Spectrophotometry Chemometrics Complexation Simultaneous analysis Multivariate calibration Interferences Partial least squares

"Quantitative Analysis Of Sulfadiazine Using Photochemically Induced Fluorescence Detection In Bulk Solution And In A Flow Injection System"
Anal. Chim. Acta 1995 Volume 314, Issue 1-2 Pages 45-50
J. J. Aaron,*, M. I. Acedo Valenzuela, M. Sanchez Pena, F. Salinas and M. C. Mahedero

Abstract: Room temperature photochemically-induced fluorescence methods were described for the determination of sulfadiazine (I). For the bulk solution method, portions of a standard solutions of I in 50% aqueous methanol were transferred to a 1 cm quartz cuvette and irradiated with a high-pressure mercury lamp for 2.5 min. The fluorescence intensity was then measured at 353 nm (excitation at 295 nm). The calibration graph was linear from 0.1-4.1 µg/ml of I and the detection limit was 40 ng/ml. The RSD (n = 10) was 1.7% for 2.6 µg/ml of I. For the FIA method, 300 µL of a standard solution containing 0.2-6.5 µg/ml of I was injected into a water carrier stream (4.2 ml/min) and passed through a photoreactor (length 250 cm) to the detector cell. The fluorescence intensity was measured at 352 nm (excitation at 295 nm). A linear calibration graph was obtained and the detection limit was 27 ng. The RSD (n = 10) was 2.1% for 2.1 µg/ml of I. The methods were applied to the determination of I in pharmaceutical preparations using a standard additions calibration procedure. Results agreed well with those obtained by an HPLC method.
Sulfadiazine Fluorescence Method comparison Photochemistry Standard additions calibration

"Photochemical Derivatization And Spectrophotometric Determination Of Thioridazine By Flow Injection"
Anal. Chim. Acta 1996 Volume 326, Issue 1-3 Pages 23-28
G. A. Rivasa, A. Mellado Romerob and J. Mart&iacute;nez Calatayuda,*

Abstract: A FIA method was developed based on the online photoderivatization of thioridazine in a 1.5 M HNO3 medium by irradiating with a germicide Hg lamp (6W, 254 nm). A 528 µL volume of the reaction mixture was injected into a 0.75 M HNO3 carrier stream (4 ml/min) and transported to the spectrophotometric detector set at 636 nm. With a detection cell path length of 1 cm, the linear calibration range was 7.5-60 ppm, the detection limit was 5 ppm and the RSD (n = 6) for 7 ppm was 2.1%. The method was applied to the determination of thioridazine in pharmaceutical preparations and relative errors of 1.4-4% were obtained.
Thioridazine Spectrophotometry Photochemistry UV reactor

"Spectrofluorimetric Flow Injection Method For The Successive Determination Of Chloroxine And Chlorquinaldol In Pharmaceutical Preparations"
Anal. Chim. Acta 1996 Volume 326, Issue 1-3 Pages 41-47
Tom&aacute;s P&eacute;rez-Ruiz*, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Jos&eacute; Carpena

Abstract: The FIA method was based on the formation of fluorescent complexes between Al(III) chloroxine (5,7-dichloroquinolin-8-ol; COX) and Cd(II) and both COX and chlorquinaldol (CQD). A sample volume of 95 µL was injected into a 14 mM SDS carrier stream (1.2 ml/min) and merged with 0.2 M acetate buffer of pH 4.2 (0.4 ml/min) and 2.5 mM Al(III) (0.4 ml/min). The Al(III)-COX complex was determined at 550 nm (excitation at 395 nm). For the combined determination of COX and CQD, a 235 µL sample volume was injected into a 18 mM cetyltrimethylammonium bromide carrier stream (1.2 ml/min) and merged with 0.2 M phosphate buffer of pH 8.3 (0.4 ml/min) and 2 mM Cd(II) (0.4 ml/min). The combined fluorescent intensity of Cd(II)-COX and Cd(II)-CQD was measured at 550 nm (excitation at 395 nm). Linear calibration graphs were obtained for 0.13-13 µg/ml COX and 0.09-13.2 µg/ml CQD and detection limits were 0.04 and 0.02 µg/ml, respectively. The RSD (n = 11) for the analysis of a mixture containing 2.5 µg/ml COX and 3 µg/ml CQD were 0.81 and 0.29%, respectively. The method was applied to the analysis of pharmaceutical preparations and the results were in agreement with manufacturers` specifications.
Chloroxine Chlorquinaldol Fluorescence Complexation Surfactant Buffer

"Flow Injection Spectrophotometric Determination Of Paracetamol In Pharmaceuticals By Means Of Online Microwave-assisted Hydrolysis And Reaction With 8-hydroxyquinoline (8-quinolinol)"
Anal. Chim. Acta 1996 Volume 330, Issue 1 Pages 59-69
Zouhair Bouhsain, Salvador Garrigues, Angel Morales-Rubio and Miguel de la Guardia*

Abstract: An automated flow injection spectrophotometric method was developed for determining paracetamol in pharmaceuticals. The method was based on the alkaline hydrolysis of paracetamol to yield p-aminophenol which was reacted with 8-hydroxyquinoline in the presence of potassium periodate oxidant to form a blue indophenol dye. An extract of the pharmaceutical preparation in 1.5 M NaOH was injected into a 1.5 M NaOH carrier stream (1.9 ml/min) via a 500 µL sample loop and passed through a reaction coil (6 m x 0.8 mm i.d.) mounted in a focused microwave cavity operating at 200 W. The flow was then merged with 4 mM KIO3 and 2.76 mM 8-hydroxyquinoline (both in 1.5 M NaOH and at 1.9 ml/min) and the absorbance was measured at 608 nm (70 µL detection cell). Calibration graphs were linear up to 158 µM-paracetamol with a detection limit of 1.25 µM and RSD (n = 5) for 39.7 µM-paracetamol of 1.9%. The method was applied to tablets, capsules, syrup and suppositories. The recoveries of 10.6-31.7 µM-paracetamol from spiked pharmaceutical formulations were 96.3-102%. The sampling frequency was 70/h.
Acetaminophen Spectrophotometry Microwave 8-Hydroxyquinoline

"Determination Of Ranitidine In Pharmaceutical Preparations Using Manual And Flow Injection Potentiometry And Spectrophotometry"
Anal. Chim. Acta 1996 Volume 332, Issue 1 Pages 39-48
Saad S. M. Hassan*, Wagiha H. Mahmoud and Abdel Hameed M. Othman

Abstract: Radine was determined by (i) manual and (ii) flow injection potentiometry using PVC membrane electrodes containing ion-association complexes of radine reineckate, tungstophosphate or tungstosilicate and 2-ophenyl phenyl ether as plasticiser solvent mediator or (iii) spectrophotometry based on the formation of di(N-nitroso)ranitidine by reaction with excess nitrite in the presence of Cu2+/Br- or micelles as catalysts. For method (i) a linear response was obtained for each electrode at pH 4-8 and detection limits were 4-95 µM-ranitidine. Method (ii) was performed by injecting 20 µL 10^-4-0.1 M ranitidine into a 5 mM NaCl carrier stream (3.3 ml/min) and measuring the potential change vs. Ag/AgCl. The RSD for 0.1 mM ranitidine was 1.1% and the average recovery of 0.35-350 mg/l ranitidine was 98.7%. Method (iii) was performed by diluting a mixture of 8.75-297.5 mg ranitidine, 5 mL 0.1 M NaNO2 and 1 mL catalyst to 25 mL with 0.1 M acetate buffer at pH 4.8 and measuring the absorbance at 450 nm. Beer's law was obeyed for 0.3-12 mg/ml ranitidine, the detection limit was 0.1 mg/ml and the RSD for 5 mg/ml ranitidine was 0.5%. The methods were applied to pharmaceutical dosage forms and recoveries were >98.2% for (i), >98.1% for (ii) and >98.3% for (iii).
Ranitidine Potentiometry Spectrophotometry Micelle Ion pair formation

"Determination Of Pharmaceutical Thiols By Liquid Chromatography With Electrochemical Detection: Use Of An Electrode With A Conductive Carbon Cement Matrix, Chemically Modified With Cobalt Phthalocyanine"
Anal. Chim. Acta 1996 Volume 332, Issue 2-3 Pages 249-255
Gabriella Favaro* and Mario Fiorani

Abstract: An electrode, prepared by doping conductive C cement with 5% cobalt phthalocyanine, was used in FIA and LC systems to detect the pharmaceutical thiols, captopril, thiopronine and penicillamine. FIA determinations were performed with phosphate buffer of pH 2 as carrier stream (1 ml/min), an injection volume of 20 µL and an applied potential of 0.6 V vs. Ag/AgCl (stainless steel counter electrode). The calibration curves were presented for 5-100 µM of each analyte. The dynamic linear range was up to ~20 µM. The detection limits were 76, 73 and 88 nM for captopril, thiopronine and penicillamine, respectively. LC determinations were performed on a 5 µm Bio-Sil C18 HL 90-5S column (15 cm x 4.6 mm i.d.) with 1 mM sodium 1-octanesulfonate in 0.01 M phosphate buffer/acetonitrile as mobile phase (1 ml/min) and gradient elution from 9:1 (held for 5 min) to 7:3 (held for 10 min) in 5 min. The working electrode was maintained at 0.6 V vs. Ag/AgCl and the injection volume was 20 µL. For thiopronine, penicillamine and captopril the retention times were 3.1, 5 and 11.3 min and the detection limits were 0.71, 1 and 2.5 µM, respectively.
Thiols Captopril Thiopronine Penicillamine LC Electrode Buffer Detector

"Flow Injection Stopped-flow Spectrofluorometric Kinetic Determination Of Paracetamol Based On Its Oxidation Reaction By Hexacyanoferrate(III)"
Anal. Chim. Acta 1996 Volume 333, Issue 1-2 Pages 59-69
J. A. Murillo Pulgar&iacute;n* and L. F. Garc&iacute;a Bermejo

Abstract: A simple and economic system, easily adaptable to any spectrophotometer or spectrofluorimeter in order to carry out kinetic measurements by means of the FIA stopped-flow technique, is described. The system consists of a 12 bit analogical digital converter that receives analogue signals at -10 and +10V and enables the electrical supply to the peristaltic pump to be interrupted. A stopped-flow method with fluorescence detection for the determination of paracetamol (N-acetyl-p-aminophenol), based on its oxidation with hexacyanoferrate(III), is described. A kinetic study of the reaction is developed measuring the initial rate of change of the fluorescence intensity of the oxidized product formed at 241 and 426 nm excitation and emission wavelengths, respectively. The calibration graph is linear in the range of concentrations 0.5-15.0 µg/ml. The relative standard deviation is 2.5%. The method was applied to authentic pharmaceutical preparations and was found to be satisfactory. The effect of same possible interferences has been studied. A stopped-flow FIA system was constructed using a microcomputer to control the movement of a peristaltic pump drum through an analogue/digital interface. Sample solution (400 µL) containing paracetamol was injected into a water carrier stream and merged with a flow of 2 M NH4Cl/NH4OH buffer of pH 8.5 and hexacyanoferrate(III) solution. The mixture was carried to a flow cell and 7 s after injection the flow was stopped for 5.8 s. The variation in fluorescence intensity was monitored at 426 nm (excitation at 241 nm) and the analyte concentration was determined using a reaction-rate concentration plot obtained under pseudo-first order kinetic conditions. The calibration graph was linear from 0.5-15 µg/ml and the RSD for the determination of 8 µg/ml of paracetamol was 2.5% (n = 10). The detection and determination limits were 0.1 and 0.3 µg/ml, respectively. The method was applied to the analysis of paracetamol in pharmaceutical preparations.
Acetaminophen Fluorescence Kinetic Stopped-flow Redox Interferences

"A New Amperometric Biosensor For Salicylate Based On Salicylate Hydroxylase Immobilized On Polypyrrole Film Doped With Hexacyanoferrate"
Anal. Chim. Acta 1997 Volume 347, Issue 1-2 Pages 35-41
Benjamin G. Milagresa, Graciliano de Oliveira Netoa, Lauro T. Kubotaa,* and Hideko Yamanakab

Abstract: An amperometric biosensor for salicylate detection was developed by immobilizing salicylate hydroxylase via glutaraldehyde onto a polypyrrole film doped with hexacyanoferrate, supported on a glassy carbon electrode surface. The sensor monitors the catechol produced in the enzymatic reaction on the film surface, at an applied potential of 150 mV vs. SCE. A / ratio between 2 and 4 gave the best response. The biosensor presented the best performance in a solution with pH=7.4. The response time was about 40 s. A linear range of response was observed for salicylate concentrations between 1.0 x 10^-5 and 1.0 x 10^-4 mol L-1 and the equation adjusted for this curve was I=(-0.04±0.01)+(11.4±0.2) with a correlation coefficient of 0.999 for n=6. The biosensor retains its activity for at least 10 days despite daily use. The results obtained using the biosensor for salicylate determination, in three different samples of antithermic drugs, presented a good correlation with the standard colorimetric method. 34 References
Salicylate Amperometry Electrode Electrode Electrode Sensor Method comparison

"Use Of PH Gradients In Continuous-flow Systems And Multivariate Regression Techniques Applied To The Determination Of Methionine And Cysteine In Pharmaceuticals"
Anal. Chim. Acta 1997 Volume 348, Issue 1-3 Pages 151-159
F. Blasco, M. J. Medina-Hern&aacute;ndez and S. Sagrado*

Abstract: The simultaneous spectrophotometric determination of methionine and cysteine in presence of cystine and other compounds in pharmaceuticals, using a multivariate calibration method, was studied. The method is based on the reaction between the analytes and the o-phthalaldehyde-N-acetyl-L-cysteine (OPA-NAC) reagent performed in a continuous-flow system (FI). The FI system allows the generation of a local pH gradient in order to produce spectral and/or kinetic changes in the W-Vis spectra of the amino acid-OPA-NAC derivatives. This information is used to improve the prediction ability of the Partial Least-Squares (PLS) models. The performance of two FI assemblies, the selection of variables and the pretreatment of the data were studied. A series of eighteen synthetic solutions containing different concentrations of methionine, cysteine and cystine was prepared and used as a calibration set to study the PLS models. In addition, solutions of a commercial formulation containing the three amino acids were prepared and the content of methionine and cysteine was predicted. The results obtained using the PLS models were compared with those obtained using an HPLC method. 13 References
Methionine Cysteine Spectrophotometry Partial least squares Multicomponent pH gradient Method comparison Multivariate calibration

"Chemiluminescence Flow Sensor For The Determination Of Vitamin-b-12"
Anal. Chim. Acta 1997 Volume 357, Issue 1-2 Pages 127-132
Wei Qin, Zhujun Zhang* and Huajun Liu

Abstract: A novel chemiluminescence (CL) sensor for vitamin B-12 combined with flow injection analysis is presented in this paper. It is based on the catalytic effect of cobalt(II), liberated from vitamin B-12 by acidification, on the CL reaction between luminol, immobilized electrostatically on an anion-exchange column, and hydrogen peroxide electrochemically generated online via a negatively-biased electrode from dissolved oxygen in the flow cell. The sensor responds linearly to vitamin B-12 concentration in the 1.0 x 10^-3-10 mg L-1 range, and the detection limit is 3.5 x 10^-4 mg L-1 vitamin B-12. A complete analysis, including sampling and washing, could be performed in 1 min with a relative standard deviation of < 3.58. The system is stable for over 500 determinations and has been applied successfully to the determination of vitamin B-12 in pharmaceutical preparations. 27 References
Vitamin B12 Chemiluminescence Ion exchange Sensor Immobilized reagent Catalysis Column

"Determination Of Iron(III) In Pharmaceutical Samples Using Dialysis In A Sequential Injection Analysis System"
Anal. Chim. Acta 1997 Volume 357, Issue 1-2 Pages 141-149
J. F. van Staden*, H. du Plessis and R. E. Taljaard

Abstract: The use of membranes for online sepns. in flow-through dialyzers as part of flow systems is extremely useful for automated sample preparation Iron (III) was separated from a sample matrix by dialysis in a sequential injection system. The dialyzed iron was complexed with tiron and the resulting complex was monitored spectrophotometrically at 667 nm. The influence of various parameters, including pump speed for both the donor and recipient streams, sample volume, reagent volume, dialysis time and the effect of multiple flow reversals, on dialysis efficiency was studied. The system was feasible for the determination of iron in pharmaceutical samples which are usually turbid and contain undissolved organic particles. The system is fully computerized and is able to monitor iron(III) in samples at a frequency of 8 samples per h with a relative standard deviation of <1.50 in the linear calibration range (100-1000 mg L-1). The 3s detection limit was 45.0 mg L-1. Although the sample frequency of the proposed sequential injection system is much lower than that of conventional flow injection systems, the volume of sample used is much smaller and the consumption of reagents is much lower, which is more cost effective. Using the feature of multiple flow reversals, the percentage dialysis can be improved to up to 4.5, which compares well with the 4 obtained with conventional flow injection anal.
Iron(III) Spectrophotometry Computer Dialysis Sequential injection

"Flow Injection Chemiluminometric Determination Of Some Phenothiazines In Dosage Forms And Biological Fluids"
Anal. Chim. Acta 1998 Volume 358, Issue 3 Pages 255-262
Fatma A. Aly, Nawal A. Alarfaj and Abdulrahman A. Alwarthan*

Abstract: A rapid and sensitive flow injection chemiluminometric method is described for the determination of three phenothiazine derivatives, namely, fluphenazine hydrochloride, levomepromazine hydrochloride and trimeprazine tartrate. The method is based on the chemiluminescence (CL) induced by the oxidation of drugs with cerium(IV) in an acidic medium. The CL intensity is greatly enhanced when rhodamine B is used as a sensitizer in the case of levomepromazine hydrochloride and trimeprazine tartrate. The proposed method allows the measurement of 0.5-90 µg mL-1 fluphenazine and 0.1-6.5 µg mL-1 levomepromazine and trimeprazine. The limits of detection (3s) were 0.01 µg mL-1 fluphenazine hydrochloride and 0.1 µg mL-1 for the other two drugs. The method was applied successfully in determining the drugs in dosage form as well as in biological fluids.
Phenothiazines Fluphenazine hydrochloride Levomepromazine hydrochloride Trimeprazine tartrate Chemiluminescence

"Online Solvent Recycling: A Tool For The Development Of Clean Analytical Chemistry In Flow Injection Fourier Transform Infrared Spectrometry. Determination Of Ketoprofen"
Anal. Chim. Acta 1998 Volume 361, Issue 3 Pages 253-260
M. J. S&aacute;nchez-Dasi, S. Garrigues, M. L. Cervera and M. de la Guardia*

Abstract: A flow injection strategy has been developed for the direct determination of ketoprofen in pharmaceuticals by Fourier transform IR spectrometry also incorporating a distillation unit which allows the carbon tetrachloride employed to dissolve samples and standards and used as a carrier to be recovered online. The system developed permits a drastic reduction of reagent consumption and easy and fast sampling and cleaning of the measurement cell. For the quantification of ketoprofen in pharmaceuticals the carbonyl bands at 1712 and 1666 cm-1 were employed and the developed method provided a 3s limit of detection of 0.04 mg mL-1, a dynamic range up to 10 mg mL-1 and typical coefficient of variation values between 1.6 and 3%, with a sample injection frequency 42 h-1. Accurate and precise results were obtained in the anal. of real pharmaceutical samples.
Ketoprofen Spectrophotometry Solvent recycling Organic phase detection

"A Multicommutated Flow System With Online Compensation Of The Schlieren Effect Applied To The Spectrophotometric Determination Of Pindolol"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 209-215
Rui A. S. Lapa*, Jos&eacute; L. F. C. Lima, Boaventura F. Reis, Jo&atilde;o L. M. Santos and Elias A. G. Zagatto

Abstract: A continuous-flow methodology for the spectrophotometric determination of pindolol in pharmaceutical preparations following complexation with Fe(III) chloride is described. The reaction is carried out within a multicommutated flow network using a binary sampling approach. The Schlieren effect, associated with the pronounced concentration. gradients in FIA system, was compensated by using a carrier solution processed online with two alternating solutions The concentration. profiles of the resulting carrier solution and the sample plug were similar, a fact that prevented the formation of concentration. gradients. Absorbance was measured at 635 nm. Beer law was followed for concentrations. up to 120 µg pindolol/mL. Results were reproducible (RSD <1.1%, n=10) and in agreement with data obtained by a reference procedure. A rate of 30 samples per h was attained.
Pindolol Spectrophotometry Complexation Multicommutation Method comparison

"Sequential Determinations By Confluent Reagent Introduction In The Sample Loop: System Characteristics And Applications"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 281-285
Andr&eacute; F. Oliveira, Orlando Fatibello-Filho*, Maria Celeste T. Diniz and Joaquim A. N&oacute;brega

Abstract: A flow injection analysis (FIA) system diagram was proposed to create two different regions in the sample zone. This was attained by introducing the reagent at a confluence point positioned in the sample loop. The two regions thus generated in the sample zone allowed the determination of two analytes. The feasibility of the system was demonstrated for the spectrophotometric determination of Fe(II) and total Fe(II+III) in pharmaceutical products. In the proposed flow diagram, the reducing reagent (ascorbic acid) was introduced in the middle of the sample loop and the chromogenic reagent (1,10-phenanthroline) was introduced at confluence before the flow cell. The flow conditions for sufficient signal resoln. were evaluated. Absorbance was measured at 520 nm. The anal. frequency attained was 40 h-1 (or 80 determinations per h since 2 species are sequentially measured in the same sample zone). The accuracy was checked by comparing with a standard batch procedure. The results obtained for pharmaceutical products were within the 95% confidence level.
Iron(2+) Iron Spectrophotometry Injection technique Sandwich technique

"Use Of Column With Modified Silica For Interfering Retention In A FIA Spectrophotometric Method For Direct Determination Of Vitamin C In Medicine"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 11-22
Julio Cesar B. Fernandes, Graciliano de Oliveira Neto and Lauro T. Kubota*

Abstract: A flow injection analysis (FIA) system with a column packed with silica modified with aminopropyl groups was used as a reactor in the spectrophotometric determination of L-ascorbic acid at 265 nm. The column (2.79 mm ID, 50 mm length) packed with modified silica (200 mg silica treated with 3-aminopropyltriethoxysilane) was used to eliminate interfering compounds by ion pair formation with amino groups. The interfering compounds studied included tartaric, citric, oxalic, and maleic acids, glucose, fructose, EDTA, Na benzoate, and Na salicylate. A processing rate of 30 samples/h, detection limit of 2.0 x 10^-6 M, and linearity range between 10^-5 and 10^-4 M were achieved in optimized conditions. The relative standard deviation was 1.5% (n=20) for a 5.0 x 10^-5 M ascorbic acid solution The method was applied to drug samples to determine ascorbic acid; the results were in agreement of the nominal values.
Ascorbic acid Spectrophotometry Silica Interferences Optimization Ion pair formation Column

"Flow Injection Spectrophotometric Determination Of L-ascorbic Acid In Pharmaceutical Formulations With Online Solid Phase Reactor Containing Copper(II) Phosphate"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 55-62
Airton Vicente Pereira and Orlando Fatibello-Filho*

Abstract: A spectrophotometric flow injection analysis (FIA) method is proposed for the determination of L-ascorbic acid in pharmaceutical formulations using the reproducibility and stability of a solid phase reactor containing copper(II) phosphate immobilized on a polyester resin matrix. The determination is accomplished by the reduction of Cu(II) ion to Cu(I), which is carried away by acetate buffer (pH 4.5) and detected by monitoring the absorbance (480 nm) of the chelate produced by the reaction between Cu(I) and bathocuproine. The calibration graph for L-ascorbic acid was linear from 5.0 x 10^-6 to 4.0 x 10^-5 M with a correlation coefficient of 0.9998. The detection limit (3-times the signal blank/slope) was 3.0 x 10^-7 M ascorbic acid. The relative standard deviation was 0.75% for 2.0 x 10^-5 M ascorbic acid (n =10) and 80 samples could be analyzed per h. The recovery of ascorbic acid from 6 samples ranged from 97.3 to 103.4% of the amt. added. The concentrations of ascorbic acid determined by the proposed FIA-spectrophotometric method were in a close agreement with data obtained with the official Pharmacopeia method.
l-Ascorbic acid Spectrophotometry Solid phase reagent Redox Indirect Method comparison Chelation

"Flow Injection Spectrophotometric Determination Of Tenoxicam"
Anal. Chim. Acta 1998 Volume 375, Issue 3 Pages 277-283
S. A. Al-Tamrah*

Abstract: A new spectrophotometric flow injection method for the determination of tenoxicam was based on the reaction of tenoxicam with iron(III) nitrate. The resulting iron(II) reacted with potassium hexacyanoferrate(III) forming a Prussian blue measurable at 724 nm. Maximum color formation was obtained through heating. The blue complex that gradually adhered to the flow lines and the flow cell walls was removed by employing an alkaline oxalate solution Linearity was in the range 0.5-100 µg mL-1 tenoxicam with a limit of detection of 0.4 µg mL-1. The method was successfully applied to the determination of tenoxicam in pharmaceuticals. The correlation coefficient was 0.99943 with a relative standard deviation of 1.04%, for 5 determinations of 5 µg mL-1 drug.
Tenoxicam Spectrophotometry Indirect

"Continuous-flow-through Solid Phase Spectrophotometric Determination Of Trace Amounts Of Zinc"
Anal. Chim. Acta 1998 Volume 375, Issue 1-2 Pages 71-80
M. J. Ayora-Ca&ntilde;ada, M. I. Pascual-Reguera and A. Molina-D&iacute;az*

Abstract: A flow-through solid phase spectrophotometric sensing device for the determination of Zn(II) was developed based on the reaction of this ion with 1-(2-pyridylazo)-2-naphthol (PAN) immobilized on a Dowex cation exchanger placed in a flow-through cell. The reaction of Zn(II) with immobilized PAN and its retention on the resin developed the analytical signal. Adequate dissociation of the Zn-PAN complex left the unaltered reagent fixed on the solid support, enabling the regeneration of the sensor. The sensor allows working with several calibration Lines simply by varying the sample volume injected for the determination. As an example, linear dynamic ranges from 0.2 to 4.0 µg mL-1 and from 20 to 500 µg L-1 can be obtained by using 100 and 2000 µl, respectively, with detection limits being 0.05 µg mL-1 and 5 µg L-1, respectively. The RSD (%) being 2.1 (100 µl) and 2.3 (2000 µl) and the sampling frequency 38 and 15 samples per hour, respectively. The sensor was applied to the determination of Zn(II) in real samples, namely, human hair, pharmaceutical and cosmetic preparations and water samples.
Zinc Spectrophotometry Optosensing Solid phase detection Linear dynamic range

"Automated Flow Injection Pseudotitration Of Strong And Weak Acids, Ascorbic Acid And Calcium, And Catalytic Pseudotitrations Of Aminopolycarboxylic Acids"
Talanta 1985 Volume 32, Issue 5 Pages 411-417
M. A. Koupparis* and P. AnagnostopoulouH. V. Malmstadt

Abstract: An automated spectrophotometric system applicable to acid - base, redox, complexometric and catalytic titrations is described. Peak widths (in time units) from 10 to 100 s can be measured with coefficient of variation of <0.3%. Strong and weak acids, both 0.5 to 20 mM, were titrated with NaOH in presence of bromothymol blue, ascorbic acid (0.1 to 10 mM) with 2,6-dichlorophenolindophenol and Ca (0.5 to 50 mM) with EDTA - Mg(II) complex and calmagite as indicator. Aminopolycarboxylic acids, EDTA and similar compounds (5 µM to 10 mM) were measured by monitoring at 470 nm the product of the manganese-catalyzed periodate diethylaniline reaction. The proposed method was applied to the determination of total hardness in water and to the determination of ascorbic acid in various pharmaceuticals.
Acids Ascorbic acid Calcium Hardness Spectrophotometry Computer Titrations Peak width

"Determination Of Levamisole Hydrochloride With Tetraiodomercurate(2-) By A Turbidimetric Method And Flow Injection Analysis"
Talanta 1986 Volume 33, Issue 8 Pages 685-687
J. Martinez Calatayud* and Campins Falco

Abstract: Sample solution (200 µL) is injected into a reagent stream (3.14 mL min-1) containing 8.55 mM Hg(I)42- (pH adjusted to 5 with phosphate - citrate buffer solution) which is then passed through a reaction coil (77 cm x 0.5 mm) resulting in the formation and precipitation of a levamisole(I) - Hg(I)42- ion-association complex (2:1); the absorbance of the suspension is measured at 430 nm. Calibration graphs are rectilinear from 7 to 32 µg mL-1 of I. In the determination of 91 µM-I, the coefficient of variation was 0.9% (n = 40). The method was used to determine I in pharmaceutical preparations also containing chlorpheniramine, giving results which agreed with those of a bromocresol purple method.
Drugs Levamisole hydrochloride Turbidimetry Sample preparation Complexation Extraction Method comparison

"Photometric And Amperometric Flow Injection Determination Of Triazolam And Clotiazepam"
Talanta 1989 Volume 36, Issue 7 Pages 761-765
R. M. Alonso*, R. M. Jimenez, A. Carvajal, J. Garcia and F. VicenteL. Hernandez

Abstract: For spectrophotometric determination, the carrier solution for triazolam (I) and clotiazepam (II) were aqueous 13% methanol and 0.1 M H2SO4, respectively, at flow rates of 5.0 and 5.4 mL min-1. Sample volume was 75 µL and delay coil dimensions were 37 cm x 0.58 mm i.d. for I and 35 cm x 0.58 mm i.d. for II. Calibration graphs were rectilinear for 3 to 55 µM-I at 228 nm and for 31 to 502 and 6 to 125 µM-II at 390 and 260 nm, respectively. For amperometric determination, the carrier solution for I and II were acetate buffer (pH 4.7) in 10% methanol and 0.1 M H2SO4, respectively, at flow rates of 4.5 and 6.4 mL min-1, sample volume were 106 and 75 µL for I and II, respectively, and delay coil dimensions were 50 cm x 0.58 mm i.d. for II and 16 cm x 0.58 mm i.d. for I. Detection was at -1.125 and -0.950 V for I and II, respectively, at a hanging-Hg-drop electrode vs. a SCE. Calibration graphs were rectilinear for 6 to 116 µM-I and 16 to 162 µM-II. Both methods were applied in the analysis of phamaceuticals.
Triazolam Clotiazepam Amperometry Electrode Spectrophotometry pH Buffer Amberlite Calibration

"Determination Of Thiamine By Continuous-flow Chemiluminescence Measurement"
Talanta 1990 Volume 37, Issue 11 Pages 1043-1048
Nikos Grekas and Antony C. Calokerinos*

Abstract: Sample solution stream was mixed with the oxidant stream of 5 mM ferricyanide solution in 1 M NaOH. The mixed stream was pumped to a spiral glass flow cell in front of a photomultiplier; the output of the photomultiplier tube was fed to an operational amplifier and then to a recorder. The effect on chemiluminescence intensity of sample and oxidant flow rates and concentration. of ferricyanide and alkali solution were investigated. Calibration graphs were rectilinear from 20 to 500 µM-thiamine nitrate or hydrochloride. The detection limit was 9 µM. In the analysis of pharmaceutical formulations, ascorbic acid interfered.
Thiamine Chemiluminescence Glass Flowcell Calibration Detection limit Interferences

"Kinetic-fluorimetric FIA Determination Of Total Ascorbic Acid, Based On Use Of Two Serial Injection Valves"
Talanta 1991 Volume 38, Issue 4 Pages 355-357
H. K. Chung and J. D. Ingle, Jr.*

Abstract: Ascorbic acid (I) samples were loaded into two serial sample injection valves and injected into a carrier system containing mercuric chloride and o-phenylenediamine; the formation of a fluorescent quinoxaline was monitored at 435 nm (excitation at 366 nm). Quinine sulfate was used to obtain calibration data. The method was compared with the single-point method using both peak height and peak area measurements. The detection limits for I in all four methods were not significantly different and ranged from 0.05 to 0.1 µg mL-1; calibration graphs were rectilinear up to at least 10 µg mL-1, and coefficient of variation were 2%. However, the two-point methods can discriminate between non-reacting interference such as the presence of fluorophore in the sample. The proposed method can cope with 30 samples h-1 and is applicable to the analysis of pharmaceutical samples.
Ascorbic acid Fluorescence Interferences Kinetic Peak analysis Dual injection

"Flow Injection Stopped-flow Kinetic Spectrophotometric Determination Of Drugs, Based On Micellar-catalysed Reaction With 1-fluoro-2,4-dinitrobenzene"
Talanta 1991 Volume 38, Issue 7 Pages 689-696
Constantinos A. Georgiou, Michael A. Koupparis* and Themistocles P. Hadjiioannou,

Abstract: Dihydralazine (I), isoniazid (II), levodopa (III) and aspartame (IV) are determined in a flow injection system in which a solution of 8.40 mM 1-fluoro-2,4-dintrobenzene in aqueous 20% ethanol acidified with 1 mM HCl was pre-mixed with 0.10 M borate buffer (pH 9.5) containing hexadecyltrimethyl-ammonium bromide (3.5 mM for I and II, 1.5 mM for III and IV) before merging with the aqueous injected sample stream. After mixing, the reaction mixture flow was stopped for 16 s followed by 2 s of mixture equilibration before multiple (40 to 256) absorbance measurements were recorded during 15 to 40 s at 428 nm for I and II and 340 and 342 nm for III and IV, respectively. The calibration graphs were rectilinear from 0.01 to 0.2 mM (III) and from 0.05, 0.01 and 0.06 to 0.6 mM (I, II and IV, respectively), and the respective detection limits were 18, 0.9, 6.3 and 20 µM for I, II, III and IV. The method, which may also be used to determine several other drugs which form soluble derivatives with the reagent, was used to determine II, III and IV in pharmaceutical formulations, II in formulations containing rifamycin, and IV in colored beverages. The results agreed well with those of reference methods.
Drugs Spectrophotometry Buffer Catalysis Detection limit Kinetic Micelle Stopped-flow Method comparison

"Simultaneous Flow Injection Determination Of Chlorpromazine And Promethazine By Photochemical Reaction"
Talanta 1991 Volume 38, Issue 11 Pages 1227-1233
Danhua Chen, A. R&iacute;os, M. D. Luque de Castro* and M. Valc&aacute;rcel,

Abstract: Chlorpromazine (I) and promethazine (II) were simultaneously determined by irradiating flow injection manifolds with UV light; the method was based on the difference in the pH of the media where the photochemical conversion of I or II into a fluorescent product took place. The choice of the best-flow injection configuration and a mathematical model for solving the mixtures are discussed. Sample throughput was 30 to 40 h-1. The coefficient of variation were 2 to 4%. The method was used to determine I and II in pharmaceuticals preparations; results agreed well with expected values.
Chlorpromazine Promethazine Fluorescence pH Photochemistry

"Determination Of Bromazepam By Coupling A Continuous Liquid - Liquid Extractor To An Atomic Absorption Spectrometer"
Talanta 1991 Volume 38, Issue 11 Pages 1241-1245
Ricardo E. Santelli, Mercedes Gallego and Miguel Valcarcel,

Abstract: Sample solution (3.2 mL min-1), containing 0.4 to 4.0 µ mL-1 of bromazepam (I) in aqueous 25% methanol, was merged with a carrier stream (0.7 mL min-1) of Cu - NaClO4 - acetate buffer (pH 4.75) and the ion-pair formed was extracted into isobutyl methyl ketone in a solvent segmenter. A portion of the extract was separated in a membrane phase separator and a 100 µL portion of the organic extract was carried by water for determination by AAS. The calibration graph was rectilinear over the cited range, the detection limit was 0.1 µg mL-1 and the coefficient of variation (n = 11) for 1 µg mL-1 of I was 1.7%. Sample throughput was 40 h-1. Recoveries from commercial pharmaceuticals were >98%.
Bromazepam Spectrophotometry Sample preparation Buffer Extraction Membrane Phase separator Organic phase detection

"Flow Injection Successive Determination Of Cysteine And Cystine In Pharmaceutical Preparations"
Talanta 1991 Volume 38, Issue 11 Pages 1235-1239
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Gabriel Lambertos

Abstract: Sample solution was merged with an aqueous hydroxylamine (1.7 mL min-1) stream, the mixture was merged with a stream of 50 µm-Hg(II) (3.0 mL min-1) at 30°C and 3.5 mM thiamine solution was added. The reaction mixture was then merged with 0.2 M phosphate buffer of pH 12 (1.7 mL min-1) and the fluorescence intensity of the resulting mixture was measured at 445 nm (excitation at 356 nm). The calibration graph was rectilinear for 10 to 100 µm-cysteine (I); the coefficient of variation (n = 11) was 1.1%. The determination of cystine (II) required previous reduction to I before analysis as above; coefficient of variation was 1.2%. The method was used to determine I and II in pharmaceuticals; results agreed well with expected values. Recoveries were 99.5 to 100.4 and 99.8 to 100.3% for I and II, respectively. Tolerance limits for interfering compounds are tabulated.
Cysteine Cystine Fluorescence Buffer Interferences

"Flow Injection Fluorimetric Determination Of Thiamine And Copper Based On The Formation Of Thiochrome"
Talanta 1992 Volume 39, Issue 8 Pages 907-911
T. Perez-Ruiz*, C. Martinez-Lozano, V. Tomas and I. Ibarra,

Abstract: Thiamine solution was injected into a stream of Cu2+ solution (2.8 mL min-1), which was then passed through a 1-m reaction coil, mixed with phosphate buffer solution (0.9 mL min-1) and passed through a second 1-m coil at 30°C. The thiochrome formed was detected fluorimetrically at 465 nm (excitation at 370 nm). Rectilinear calibration was obtained for 0.3 to 6.0 µg mL-1 of thiamine or, by injection of a standard volume of thiamine solution, for 0.5 to 5.0 µg mL-1 of Cu. The method was applied to the determination of thiamine in pharmaceuticals and of Cu in alloys and ores. Other vitamin B components interfered with the determination of thiamine, and other transition metals with that of Cu; I- interfered in both methods. The reaction, involving the oxidation of thiamine by copper(II) in basic solutions to fluorescent thiochrome, has been adapted to the determination of thiamine by flow injection analysis Linear calibration graphs are obtained between 0.30 and 6.02 µg/mL with a sampling rate of 50 samples/h and a relative standard deviation of 0.53%. This reaction has also been adapted to the determination of copper(II) over the range 0.5-5.0 µg/mL. The applicability of both methods for determination of thamine and copper is demonstrated by investigating the effect of potential interferences and by the anal. of real samples (pharmaceuticals for thiamine and ores and allows for copper).
Thiamine Copper Fluorescence Heated reaction Interferences

"Flow Injection Method For The Assay Of The Antiarrhythmic Procainamide Hydrochloride In Drug Formulations Utilizing Statistical Optimization Techniques"
Talanta 1993 Volume 40, Issue 5 Pages 623-627
Salah M. Sultan and Fakhr Eldin O. Suliman,

Abstract: A flow injection spectrophotometric method based on the oxidation of procainamide HCl with Ce(IV) in H2SO4 and subsequent monitoring of the absorbance at 480 nm was used to determine procainamide HCl in proprietary drugs. The Factorial Design program was used to examine the significance of H2SO4 concentration, Ce(IV) concentration, sample loop size, flow rate and coil length on the sensitivity and conditions were optimized by the Super Modified Simplex program. Calibration graphs were linear over the range 100 to 600 ppm, the coefficient of variation (n = 5) was 0.5% and the sampling rate was 250 h-1. The optimized system requires no pretreatment or extraction processes, suffers no interferences, has a short analysis time and high precision and is suitable for micro-analysis of the drug.
Procainamide hydrochloride Spectrophotometry Optimization Simplex Redox Factorial design Interferences

"Flow Injection Titrimetric Analysis Of Vitamin C In Pharmaceutical Products"
Talanta 1993 Volume 40, Issue 5 Pages 593-598
Salah M. Sultan

Abstract: A method for determining ascorbic acid is described, based on its oxidation to dehydroascorbic acid with Ce(IV) in H2SO4 solution and monitoring the decrease in absorbance in a self-indicating system. Ascorbic acid solution was injected into a carrier stream (5 mL min-1) of 7.48 mM Ce(IV) in 0.1 M H2SO4 and the resulting solution was dispersed in a mixing chamber, propelled through a flow-through cell and detected spectrophotometrically at 410 nm. The method was applicable between 0.06 and 0.17 M ascorbic acid with a sampling frequency of 36 h-1 and coefficient of variation (n = 5) of 0.9. The system is simple, does not require an indicator, suffers no interferences and is sufficiently accurate for the determination of ascorbic acid in proprietary drugs.
Ascorbic acid Spectrophotometry Redox Interferences Titrations

"Computer-assisted Optimization Of A Flow Injection Method For The Assay Of Promethazine, Chlorpromazine And Trimeprazine In Drug Formulations"
Talanta 1993 Volume 40, Issue 5 Pages 681-686
Salah M. Sultan

Abstract: The cited neuroleptics were oxidized by K2Cr2O7 in H2SO4 and determined by flow injection spectrophotometry at 515, 526 and 510 nm, respectively. Optimum conditions for max. absorbance were obtained by varying the dichromate and acid concentration. together with the flow rate and reaction coil length using the modified simplex computer program (optimum conditions for each drug given). A 110 µL sample volume was used and a high sample throughput of 200 h-1 was obtained for all compounds. Beer's law was obeyed between 40 and 280 ppm of promethazine. Acceptable coefficient of variation (0.4 to 0.9%) and good accuracies (99.5 to 99.9%) were attained with no interferences when the method was statistically compared with the British Pharmacopoeia method for the analysis of proprietary drugs.
Promethazine Chlorpromazine Trimeprazine Spectrophotometry Optimization Computer Interferences Simplex Method comparison

"Atropinium Scopolaminum Integrated Microconduits In A Potentiometric Analytical System"
Talanta 1993 Volume 40, Issue 9 Pages 1445-1448
Cui Hongbo

Abstract: The preparation of the flow-through tubular atropinium and scopolaminum electrodes and assemblage of the integrated microconduit potentiometric analytical system with tubular ISEs, microvalve, manifold, electrostatic and pulse inhibitors are described. Electrochemical characteristics of new atropinium scopolaminum integrated microconduit FIA-ISEs were studied, The contents of atropine and scopolamine in drugs could be determined at almost equilibrium state at sampling rates of 120/hr. The standard deviation over the linear range was about 0.1 mV (N = 11). A FIA-ISE manifold for the determination of atropine and scopolamine in drugs is described based on flow-through tubular atropinium and scopolaminum electrodes. The tubular electrodes were prepared by replacing a small part of the wall of PVC tubing (0.5 mm i.d., 1.5 mm o.d.) with 0.25 mm2 of the corresponding sensor membrane (prepared from 1% atropimium-tetraphenylboron or scopolaminum-tetraphenylboron, 68% dibutyl phthalate, 31% PVC). The PVC tube was then mounted in a Perspex housing and surrounded with 0.1 M NaCl/10 mM atropinium or scopolaminum saturated with AgCl into which a Ag/AgCl wire was inserted. This tube acted as the detector and the potential was recorded vs. a Ag/AgCl placed in a side channel also fed by a stream of carrier solution of 0.05 M magnesium acetate. The flow-rate through the detector and reference channel are 1.2 and 0.24 ml/min, respectively. The response of the electrodes was linear for 0.02-100 mM for atropine and scopolamine with a response time of 15 sec and a sampling rate of ~120/h. The detection limits are 2 µM atropine and 4 µM scopolamine with recoveries of 98-102%.
Atropinium Scopolamine Potentiometry Electrode Electrode Electrode Apparatus Detector Microfluidic

"Application Of Photochemical Inhibition In Flow Injection Systems: Determination Of Epinephrine And L-dopa"
Talanta 1993 Volume 40, Issue 11 Pages 1625-1630
T. P&eacute;rez-Ru&iacute;z, C. Mart&iacute;nez-Lozano, V. Tom&aacute;s and O. Val,

Abstract: The determination of epinephrine (adrenaline; I) and dopa was based on the strong inhibition of these catecholamines on the photo-reduction of phloxin by EDTA which was monitored by the fluorescence intensity of the dye. The FIA manifold allowed the sample solution to be mixed with 50 µM-phloxin solution in 0.1 M phosphate buffer of pH 6 (1:1) and 185 µL of this mixture to be injected into a carrier stream (1.5 ml/min) of 0.1 M EDTA at pH 6. The mixture was then passed through a PTFE reaction coil (200 cm x 0.5 mm i.d.) which was irradiated with a halogen quartzline lamp and onto the spectrofluorimetric detector cell. The fluorescence intensity was measured at 543 nm (excitation 530 nm). The calibration graphs were linear for 1.9-26.4 µg/ml for I and 1.5-12.7 µg/ml for dopa. The RSD (n = 10) for 3.3 µg/ml of I and 1.9 µg/ml of dopa were 1% and 0.6%, respectively, with a sampling frequency of 35 samples/h. The recovery of I (3.4-10.2 mg/ml) and dopa (1-2 mg/ml) from spiked pharmaceutical preparations was >97.7%.
l-Dopa Epinephrine Fluorescence Photochemistry Redox EDTA

"Kinetic Study Of The Degradation Of Chlorpyrifos By Using A Stopped-flow FIA System. Semi-automatic Determination In Commercial Formulations"
Talanta 1994 Volume 41, Issue 5 Pages 651-657
A. Espinosa-Mansilla*, F. Salinas and A. Zamoro,

Abstract: The stopped-flow system consisted of a peristaltic pump, diode-array detector, and computer. A 50 µL portion of 40% ethanolic sample solution containing up to 2.63 µg of chlorpyrifos (I) was injected into the carrier stream comprising 0.5 M NaOH/40% ethanol/0.55 g/l of H2O2. The reaction was monitored at 328 nm. The method was used to determine I in a liquid commercial formulation. The calibration graph was linear up to 0.2 mM I with a detection limit of 6.6 µM-I.
Chlorpyrifos Spectrophotometry Stopped-flow Kinetic

"Novel Ferroin Membrane Sensor For Potentiometric Determination Of Iron"
Talanta 1994 Volume 41, Issue 6 Pages 891-899
Saad S. M. Hassan* and Sayed A. M. Marzouk,

Abstract: Sodium tetraphenylborate solution (10 mM) and 10 mM ferroin [tris-(1,10-phenanthroline)iron(II)] were mixed for 5 min and the precipitate was collected, washed with water, dried for 24 h and finely ground. The powder was mixed with 2-nitrophenyl phenyl ether, PVC and THF, the solvent evaporated overnight and the resulting 0.1 mm thick membrane was fitted into a sandwich FIA cell. A Ag/AgCl internal reference wire electrode was immersed in a 10 mM ferroin/10 mM NaCl (1:1) internal reference solution The test solution was injected into a stream of 5 mM 1,10-phenanthroline and 10% hydroxylammonium chloride in 0.1 M acetate buffer of pH 4.7 in a FIA system, the solution passed through a mixing coil into a sandwich cell. The calibration graph was linear for 1-100 µM-ferroin, allowing the determination of total Fe. Fe(II) was determined batchwise by the omission of the hydroxylammonium chloride and the addition of EDTA. The removal of interfering anions is discussed. The method was applied to the determination of Fe in tap, underground, sea and mineral water, Al- and Cu-based alloys, cement, rocks and pharmaceutical preparations (details given). The recovery of 300 µg of Fe was 101.9% with RSD (n = 10) of 1.1%.
Iron Electrode Sensor Potentiometry Membrane Interferences

"Flow Injection Extraction-spectrophotometric Determination Of Imipramine In Pharmaceuticals With Methyl Orange"
Talanta 1994 Volume 41, Issue 9 Pages 1523-1527
Tom&aacute;s P&eacute;rez-Ruiz*, Carmen Martinez-Lozano, Antonio Sanz and Carmen Alonso,

Abstract: Imipramine in aqueous solution is extracted into 1,2-dichloroethane as its ion-pair with Methyl Orange in an unsegmented flow system and quantified spectrophotometrically. A linear calibration graph was obtained between 0.79 and 25.3 µg/ml of imipramine. Up to 45 samples/hr can be processed with a RSD of 0.88-1.6%. The method was satisfactorily applied to the determination of imipramine in pharmaceutical preparations.
Imipramine Spectrophotometry Sample preparation Extraction

"Chemiluminescence Detection Of Sodium Nitroprusside Using Flow Injection Analysis"
Talanta 1994 Volume 41, Issue 10 Pages 1683-1688
Abdulrahman A. Alwarthan,

Abstract: Sodium nitroprusside (I) was injected into a stream of 0.01 M luminol in 0.1 M carbonate buffer of pH 10.4 (2.5 ml/min) which passed through a reaction coil (150 cm x 0.8 mm i.d.) in a water bath at 70°C. The stream merged with a 1 mM H2O2 stream (2.5 ml/min), mixed in a PTFE T-piece and passed into a coiled glass flow cell (5 turns; 1.3 mm i.d.). Chemiluminescence was detected by a photomultiplier tube. The calibration graph was linear for 0.05-10 µg/ml of I with a detection limit of 0.05 µg/ml and RSD (n = 10) of 1.18% for 2.5 µg/ml. The effects of foreign cations and other excipients found in pharmaceuticals are tabulated and discussed. The method was used for the determination of I in pharmaceutical preparations.
Nitroprusside Chemiluminescence Heated reaction

"Fluorimetric Determination Of Phenothiazine Derivatives By Photooxidation In A Flow Injection System"
Talanta 1994 Volume 41, Issue 11 Pages 1985-1989
Belkacem Laassisa, Jean-Jacques Aarona,* and Maria Carmen Mahederob,

Abstract: Flow-injection analysis (FIA) was combined with photochemically induced fluorescence (PF) detection for the determination of four phenothiazine derivatives, including unsubstituted phenothiazine, thionine, Azure A and Methylene Blue. The working analytical parameters (flow-rate, injected volume, photoreactor length) were optimized. Linear calibration graphs were obtained over about two orders of magnitude, with relative standard deviation within the range 1-2.3%. Limits of detection were between 13 and 35 ng/ml, according to the compound. The FIA-PF method was applied to the determination of phenothiazines in urine samples. Mean recoveries ranged from 94 to 117%.
Phenothiazine, derivatives Fluorescence Photochemistry

"Determination Of Ascorbic Acid In Soft Drinks, Preserved Fruit Juices And Pharmaceuticals By Flow Injection Spectrophotometry: Matrix Absorbance Correction By Treatment With Sodium Hydroxide"
Talanta 1995 Volume 42, Issue 6 Pages 779-787
Archana Jain, Anupama Chaurasia and Krishna K. Verma*

Abstract: Schematic diagrams of two flow injection systems for the spectrophotometric determination of ascorbic acid at 245 nm are presented. On treatment with NaOH, a fraction of the ascorbic acid was decomposed into substances which do not absorb in the UV region, and the decrease in signal, which was directly related to the amount of ascorbic acid present, was measured. The calibration graph was linear from 1-25 and 1-50 µg/ml using the two methods. Corresponding detection limits were 0.5 and 0.2 µg/ml, respectively. RSD for 1 µg/ml were 2.5 and 1.8%, respectively, (n = 6) and the sampling throughput was 30/h. The methods permitted the use of 6 µg/ml of 2-mercaptoethanol as an anti-oxidant and stabilizer for ascorbic acid. Recoveries were 101%. Results compared well with those from standard methods.
Ascorbic acid Spectrophotometry Method comparison Standard method

"FIA-AAS Determination Of Salicylic Acid By Solid-phase Reactor Of Copper Carbonate Incorporated In Polyester Resin Beads"
Talanta 1995 Volume 42, Issue 9 Pages 1285-1289
G. A. Rivas and J. Mart&iacute;nez Calatayud*,

Abstract: The determination was carried out by reaction of salicylic acid with copper carbonate entrapped in a polymeric material in a solid-phase reactor; the released Cu(II) ions were monitored by flame AAS at 324.8 nm. A diagram of the continuous-flow manifold is given. Cu(CO3)Cu(OH)2.10H2O (Panreac, 45 g) was added to 15 g of resin solution AL-100 A (Reposa). After homogenization by manual stirring, 1 mL catalyst (ethyl methyl ketone; Azko) was added. The resultant solid was reduced to small particles, washed with water and dried at 80°C. The particles, selected by size (90-200 µm) were washed and introduced into the solid-phase bed reactor, which was constructed of PTFE tubing (5 cm x 1.2 mm i.d.). Pharmaceuticals containing salicylic acid were either dissolved in water or ethanol, diluted with water and injected into the FIA manifold. The calibration graph was linear from 4-75 µg/mL and RSD were 1.5%. Sample throughput was 257/h. The effect of foreign compounds is tabulated.
Salicylic acid Spectrophotometry Solid phase reagent Indirect Interferences Resin

"Inorganic Tin(II) Determination By FIA With Amperometric Detection Of Its Oxinate Complex"
Talanta 1995 Volume 42, Issue 12 Pages 1883-1890
K. Boutakhrit, Z. P. Yang and J. -M. Kauffmann*

Abstract: A highly selective, rapid and direct amperometric method, based on the formation of a complex between tin(II) and 8-hydroxyquinoline (oxine). has been developed for the determination of trace levels of tin(II) using flow injection analysis. Tin(II) electro-oxidation was catalyzed by oxine; its oxidation peak occurred at +0.05 V vs. Ag/AgCl at a glassy carbon electrode in 0.1 mol L-1 acetate buffer (pH 6). A linear relationship was obtained between the peak current and the tin(II) concentration in the range 0.25-20 µmol l-1. The detection limit was 0.1 µmol L-1 and the relative standard deviation calculated by the injection of a 10 µmol L-1 tin(II) solution was 5% (n = 20). Optimization of several experimental parameters has been carried out and the influence of numerous cations and possible interfering molecules encountered in radiopharmaceuticals and in dental gels has been investigated. The method was applied to the determination of tin(II) in dental gels. (54 References)
Tin(II) Amperometry Electrode 8-Hydroxyquinoline Complexation Interferences Optimization

"Sequential Injection Technique Employed For Stoichiometric Studies, Optimization And Quantitative Determination Of Some Fluoroquinolone Antibiotics Complexed With Iron(III) In Sulfuric Acid Media"
Talanta 1996 Volume 43, Issue 4 Pages 559-568
Fakhr Eldin O. Suliman and Salah M. Sultan*

Abstract: The sequential injection apparatus described previously (cf., Analyst, 1995, 120, 561) was used. All solutions were adjusted to a constant ionic strength of 0.2 M with ammonium sulfate. In the study to determine the stoichiometry and formation constants of the Fe(III) complexes by Job's method and the molar ratio method, a series of reagent and drug solutions was nested round the selector valve, with 10 ports, so that a number of experiments could be carried out rapidly. For analytical purposes, the lines were cleared by pumping 5 mM H2SO4 for 25 s (29.5 µL/s) in the forward direction. Then 147.5 µL of 1 mM ferric ammonium sulfate solution and 88 µL drug solution were pumped into the holding coil (1.5 m x 0.8 mm i.d.) with reverse flow. Finally the carrier solution transported the reactants via a reaction coil (0.5 m x 0.8 mm i.d.) to the detector. The complexes of ciprofloxacin and norfloxacin were detected at 447 and 430 nm, respectively. Calibration graphs were linear for 50-500 ppm ciprofloxacin and 50-400 ppm norfloxacin. The method was applied to tablets and infusions. The results were 99.4-101.8% of the declared amounts with RSD of 0.55-1% (n = 5).
Ciprofloxacin Norfloxacin Spectrophotometry Optimization

"Flow Injection Spectrophotometric Determination Of Ascorbic Acid In Pharmaceutical Products With The Prussian Blue Reaction"
Talanta 1996 Volume 43, Issue 6 Pages 971-976
Joaquim A. N&oacute;brega* and Gisele S. Lopes

Abstract: Liquid pharmaceuticals were dissolved in 14 mM nitric acid and injected into a carrier stream (4 ml/min) of 14 mM nitric acid which merged with a reagent stream (1 ml/min) of 1 mM iron(III) nitrate in 14 mM nitric acid. After passing through a reaction coil (150 cm), a reagent stream (1 ml/min) of 5 mM potassium ferricyanide was merged with the resulting stream and passed through a second reaction coil (100 cm). The blue complex formed was measured at 700 nm. The flow cell was cleaned during the sampling mode by an intermittent flow (1 ml/min) of alkaline oxalate solution. Calibration graphs were linear for 5-100 µM-ascorbic acid with a RSD (n = 10) of 1%. Results agreed well with those obtained by the flow injection procedure for the reaction between triiodide and ascorbic acid.
Ascorbic acid Spectrophotometry

"Automatic Extraction-spectrophotometric Method For The Determination Of Ambroxol In Pharmaceutical Preparations"
Talanta 1996 Volume 43, Issue 7 Pages 1029-1034
Tom&aacute;s P&eacute;rez-Ruiza,*, Carmen Mart&iacute;nez-Lozanoa, Antonio Sanza and M. Teresa San Miguela

Abstract: Ambroxol was dissolved in water and injected into a carrier stream (0.8 ml/min) of 0.5 M acetate buffer of pH 4. The carrier stream merged with a reagent stream (0.8 ml/min) of 0.6 mM bromothymol blue and passed through a reaction coil (30 cm x 0.5 mm i.d.). The resulting stream merged with a reagent stream (2 ml/min) of 1,2-dichloroethane at a segmentor, the stream passed through an extraction coil (150 cm x 0.5 mm i.d.) to a phase separator. The absorbance of the organic phase was measured at 420 nm. The calibration graph was linear from 8-400 µM-ambroxol with a detection limit of 0.5 µM and RSD (n = 10) of 0.88% for 10 µM and 0.32% for 80 µM. The method was used to determine ambroxol in pharmaceuticals with recoveries of 97.2-102.6%. Excipients did not interfere.
Ambroxol Spectrophotometry Sample preparation Extraction Buffer Interferences Phase separator

"Amperometric Flow Injection Method For The Assay Of L-ascorbic Acid Based On The Photochemical Reduction Of Methylene Blue"
Talanta 1996 Volume 43, Issue 8 Pages 1275-1279
Luis E. Le&oacute;n*

Abstract: Vitamin C tablets were dissolved in 0.1 M HClO4, filtered and the filtrate diluted with 0.1 M HClO4. The solution was further diluted with 0.1 M phthalate buffer to give a pH of 3.8. The sample solution was injected into a carrier stream (2.2 ml/min) of Methylene Blue in 0.1 M phthalate buffer of pH 3.8. The stream passed into a water bath at 32°C where it was irradiated with a 500 W halogen lamp in a reactor (150 cm x 0.5 mm i.d. coiled tube). The ascorbic acid was measured by amperometry with a vitreous carbon electrode, a Pt wire auxiliary electrode and a 3 M KCl Ag/AgCl reference electrode. Calibration graphs were linear for 5-90 µg/ml ascorbic acid with a detection limit of 1.9 µg/ml and a RSD (n = 9) of 1.3-4.8%.
Ascorbic acid Amperometry

"Potentiometric Flow Injection Determination Of Amylase Activity By Using Hexacyanoferrate(III)-hexacyanoferrate(II) Potential Buffer"
Talanta 1998 Volume 45, Issue 3 Pages 565-573
Hiroki Ohuraa, Toshihiko Imatob,*, Yasukazu Asanoc and Sumio Yamasakia

Abstract: A highly sensitive potentiometric flow injection determination of amylase activity was carried out, utilizing a redox reaction of hexacyanoferrate(III) in alkaline media with reducing sugar as product of the enzymatic hydrolysis reaction of starch with amylase. The analysis method is based on the potential change detection of a flow-through type redox electrode detector due to the composition change of a [Fe(CN)6]3--[Fe(CN)6]4- potential buffer solution, which is caused by the redox reaction with the product of the enzymatic reaction. A linear relationship exists between the potential change (peak height) and the activity of amylase. Amylase of a wide activity range from 2.5 x 10^-2 to 1.2 x 10^-4 U mL-1 can be determined by the changing the concentrations of the [Fe(CN)6]3--[Fe(CN)6]4- potential buffer from 10^-3 to 10^-5 M. The lower detection limit of amylase activity is 6.0 x 10^-5 U mL-1. The sampling rate and relative standard deviation are 15 h-1 and 0.9% (n = 5) for 3.8 x 10^-3 U mL-1 of amylase. The present method was successfully applied to determine amylase activity in real samples (commercial digestive medicines) with an accuracy of 4% compared with analytical results obtained using the present method with those achieved using the conventional titration method.
α-Amylase Potentiometry Redox Method comparison Indirect

"ByT-FAS (bypass Trapped-flow Analysis System)"
Talanta 1998 Volume 45, Issue 3 Pages 493-505
Kent K. Stewart* and Stephen W. Hillard

Abstract: A new semi-automated flow analysis system called bypass trapped flow analysis system (ByT-FAS) is described. ByT-FAS gives an analyst the ability to inject sample and reagent volumes of 50-100 µL or more into flowing streams and attain phys. steady state concentrations. in the detection cell within a few seconds (<1 min) after the insertion of the sample and/or reagent. After phys. steady state is attained, the system flow is diverted around the detection cell and the reaction mixture is trapped in the detector. The concentration. of the analyte and the reagent in the detection cell can be readily computed from knowledge of the original concentrations of the analyte sample and reagents and knowledge of the flow rates of the streams propelling the analyte and the reagents. ByT-FAS was demonstrated to be useful for direct measurements of analytes in liquid solutions and for assays which utilize equilibrium. and/or kinetic chemistries to create measurable product(s) using UV/visible spectrophotometry. Enzyme activities and fundamental enzyme kinetic parameters (KMs, KIs, kcats, etc.) were determined directly. The ByT-FAS instrumentation, as described, can be used interchangeably for either equilibriumibrium or kinetic assays. It is believed that this new type of instrumentation will be of significant use for the analytical chemistry, biochemistry, molecular biology, biotechnology, environmental, pharmaceutical and medical communities.
Spectrophotometry Bypass trapped Detector Steady state Kinetic Stopped-flow

"Chemometrical Optimization FIA Of Perphenazine Assay"
Talanta 1998 Volume 46, Issue 5 Pages 897-906
Salah M. Sultan* and Anthony D. Walmsley

Abstract: A flow injection analysis (FIA) method for the determination of perphenazine using cerium(IV) as an oxidant in a sulfuric acid medium was developed. The optimum anal. conditions were 0.170 M sulfuric acid, 2.13 mM cerium(IV) sulfate, 2.56 mL/min flow rate, 52 cm coil length, 136 µL sample loop size, and absorbance measurement at 525 nm. Anal. of the response surface revealed the presence of a broad max. around the simplex method optimum. A linear calibration curve in the range of 50-500 ppm, sampling frequency at least 120/h, and a relative standard deviation of <0.8% were obtained for the determination of perphenazine in its pure anal. grade form. Perphenazine determination in pharmaceutical preparations indicated that the method does not suffer from excipient interferences and is suitable for perphenazine assays in drug formulations.
Perphenazine Spectrophotometry Chemometrics Optimization Interferences Simplex Response surface

"Flow Injection Spectrophotometric Determination Of Calcium Using Murexide As A Color Agent"
Talanta 1998 Volume 46, Issue 6 Pages 1245-1257
Kate Grudpana,*, Jaroon Jakmuneea, Yuthsak Vaneesorna, Surasak Wataneska, U Aye Maung, a and Ponlayuth Sooksamitib

Abstract: FI spectrophotometric determination of Ca using murexide was developed. The problem of the color of the dye fading and/or its complex in an alkaline medium in the batch method can be overcome by taking advantage of FIA. A Ca solution is injected into an ethylenediamine-ethylenediamine hydrochloride buffer (1 M, pH 11) which also serves as a masking agent, and is then merged with the aqueous murexide (0.005%, wt./v) and continuously monitored. Simple FIA manifolds, including an LED colorimeter detector hooked up to a PC-based data acquisition and evaluation system are described. Optimization of FIA systems was made. The proposed procedures were validated by using reference materials and comparing the results with the standard methods, and then applied to ores and drug samples.
Calcium Spectrophotometry Buffer Light emitting diode Computer Optimization Method comparison

"Spectrophotometric Flow Injection Determination Of L-ascorbic Acid With A Packed Reactor Containing Ferric Hydroxide"
Talanta 1998 Volume 47, Issue 1 Pages 11-18
Airton Vicente Pereira and Orlando Fatibello-Filho*

Abstract: A flow injection system with spectrophotometric detection is proposed for determining L-ascorbic acid in pharmaceutical formulations. In this system a column containing Fe(OH)3 immobilized in polyester resin (packed reactor) is inserted before the detector. Fe(III)-1,10-phenanthroline complex was reduced by L-ascorbic acid to produce Fe(II)-1,10-phenanthroline complex which was monitored at 510 nm. Under the optimum anal. conditions, the linearity of the calibration equation for L-ascorbic acid ranged from 5.0 x 10^-6 to 6.0 x 10^-5 M of added amt. The detection limit was 5.0 x 10^-7 M and recoveries between 98.5-102.0% were obtained. No interference was observed from the common excipients of pharmaceutical formulations and other active substances such as acetylsalicylic acid, caffeine and thiamine.
l-Ascorbic acid Spectrophotometry Solid phase reagent Redox Optimization Interferences Indirect

"Flow Injection Spectrophotometric Determination Of Metoclopramide Hydrochloride"
Talanta 1998 Volume 47, Issue 1 Pages 223-228
M. Royo Herrero, A. Mellado Romero and J. Mart&iacute;nez Calatayud*

Abstract: Metoclopramide was spectrophotometrically determined in pharmaceuticals by the Bratton-Marshall method in a flow injection assembly. The required nitrite was prepared online in the flow assembly by reducing a nitrate solution with the aid of a copper-cadmium solid phase reactor. The calibration graph was linear over the range 0.5-85 mg L-1, with a relative standard deviation of 0.89%, and sample throughput of 51 samples h-1. The method eliminates the need for frequent preparation of unstable nitrite solutions.
Metoclopramide hydrochloride Spectrophotometry Solid phase reagent Reduction column

"Permanganate-based Chemiluminescence Analysis Of Cefadroxil Monohydrate In Pharmaceutical Samples And Biological Fluids Using Flow Injection"
Talanta 1998 Volume 47, Issue 2 Pages 471-478
Fatma A. Aly, Nawal A. Alarfaffj and Abdulrahman A. Alwarthan*

Abstract: A chemiluminescent method using flow injection is described for the determination of cefadroxil monohydrate. The method is based on the chemiluminescence reaction of cefadroxil with potassium permanganate in sulfuric acid, sensitized by quinine. The proposed procedure allows the determination of cefadroxil over the concentration. range 0.1-30 µg mL-1 with a detection limit of 0.05 µg mL-1 and a sample measurement frequency of 150 samples h-1. The method was successfully applied to the determination of cefadroxil in pharmaceutical preparations and biological fluids.
Cefadroxil Chemiluminescence

"Determination Of Phenylpropanolamine And Methoxamine Using Flow Injection With Fluorimetric Detection"
Talanta 1998 Volume 47, Issue 2 Pages 455-462
P. Vi&ntilde;as, C. L&oacute;pez-Erroz, F. J. Cerd&aacute;n and M. Hern&aacute;ndez-C&oacute;rdoba*

Abstract: A new flow injection procedure for the determination of phenylpropanolamine and methoxamine is proposed. The method is based on the derivatization reaction of the primary amine group with o-phthalaldehyde in the presence of 2-mercaptoethanol using fluorometric detection. The calibration graphs based on peak areas were linear in the ranges 5-200 ng mL-1 for phenylpropanolamine and 0.2-6 ng mL-1 for methoxamine. The detection limits were 3.8 and 0.13 ng mL-1, respectively. The methods were applied to the determination of the drugs in commercial pharmaceutical preparations.
Phenylpropanolamine Methoxamine Fluorescence

"Indirect Spectrophotometric Determination Of Ascorbic Acid With Ferrozine By Flow Injection Analysis"
Talanta 1998 Volume 47, Issue 3 Pages 531-536
A. Molina-D&iacute;az*, I. Ortega-Carmona and M. I. Pascual-Reguera

Abstract: A FIA indirect spectrophotometric determination of ascorbic acid was developed using its reducing action on Fe(III) in acidic medium and following the spectrophotometric determination of the reduced iron by using sodium 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine-4',4''-disulfonate (ferrozine) as chromogenic reagent in buffered medium (pH 5.5) and monitoring the absorbance signal at 562 nm. A three-line manifold with two reaction coils was used: in the first reaction coil, ascorbic acid reduces Fe(III) to Fe(II); and in the second one, the complexation reaction is developed. The linear range of the method was 0.5-10 µg mL-1 of ascorbic acid, the detection limit being 0.028 µg mL-1. The proposed method was sensitive, rapid (sampling rate of 90 samples h-1) and reproducible (RSD 0.19%, n = 10). Satisfactory results were obtained in the determination of ascorbic acid in pharmaceutical preparations, fruit juices and urine testifying the applicability of the method to real samples.
Ascorbic acid Spectrophotometry Indirect Complexation

"Fluorescence And Chemiluminescence Determination Of Steroid And Bile Acid Sulfates With Lucigenin By Flow Injection Analysis Based On Ion-pair Solvent Extraction"
Analyst 1985 Volume 110, Issue 6 Pages 665-668
Masako Maeda and Akio Tsuji

Abstract: A flow injection analyzer. with a PTFE membrane as phase separator and a chemiluminescence detector was constructed for the cited determination. Steroid sulfates were extracted into the organic phase through the separator with lucigenin, the resulting ion pair solution was mixed with alkaline H2O2 solution and the chemiluminescence was measured by a detector equipped with a spiral coil cell. The rectilinear calibration graphs were reproducible when samples of 3 to 30 or 75 to 600 pmol of steroid sulfates were injected for chemiluminescence or fluorescence detection, respectively, and the detection limits were 0.5 and 25 pmol. Fluorescence was measured at 480 nm (excitation at 365 nm). Steroid glucuronides, bile acid 3-O-sulfates and bile acids were also detected by this system.
Steroid, glucuronides Steroid, sulfates Bile acid, sulfates Chemiluminescence Fluorescence Sample preparation Flowcell Phase separator Teflon membrane Solvent extraction

"Application Of Gradient Flow Injection Analysis To Studies Of Drug-protein Binding"
Analyst 1985 Volume 110, Issue 10 Pages 1271-1272
G. L. Abdullahi and James N. Miller

Abstract: Drug - protein binding interactions and other non-covalent equilibria between small molecules and proteins are of great importance in analytical chemistry, immunochemistry, pharmacology and related fields.1 They are best investigated by measuring changes in spectroscopic or other properties that accompany the binding reaction. Such "homogeneous" methods avoid the need to separate bound and unbound drug molecules once equilibrium is established, and are thus conveniently automated. In the authors' laboratory, merging zone flow injection analysis (FIA) with fluorescence detection was applied to investigations of the protein binding of acidic and basic drugs: the detector monitored the enhanced fluorescence of probe molecules competing with the drugs for protein binding sites. These studies used medium-dispersion FIA, the required range of drug to protein concentration ratios being obtained by separate injections of drug and protein solutions of different concentrations.
Drugs Clinical analysis Fluorescence Gradient technique

"Flow Injection Analysis Of Three N-substituted Phenothiazine Drugs With Amperometric Detection At A Carbon Fiber Array Electrode"
Analyst 1985 Volume 110, Issue 12 Pages 1493-1496
Fathalla Belal and James L. Anderson

Abstract: The cited rod electrode was formed by embedding a multi-strand carbon-fiber yarn in Epon 828 resin (Miller Stephenson, Chicago, USA) - m-phenylenediamine (43:7). The active end of the array was sanded and polished. The detector cell was of the three-electrode, fully developed wall-jet design, and the mobile phase (1.0 mL min-1) was methanol - phosphate buffer of pH 7 containing 2% of Na acetate (1:1). Samples of perphenazine(I), fluopromazine hydrochloride(II) and fluphenazine hydrochloride(III), in the cited mobile phase, were injected into the electrolyte stream, and the current was measured at +1.1 V (vs. silver - AgCl - 3.5 M KCl). The graph of current vs. concentration. was rectilinear over the range 1 to 50 µg mL-1 for each drug. Good reproducibility was obtained; coefficient of variation (peak heights) were 0.8%, 0.95% and 1.2%, respectively, for 50 µL injections of 20 µg mL-1 of III, I and II. The detection limits were 5 ng mL-1. Sampling rates of up to 200 h-1 were achieved. The method has been used to determine I, II and III in dosage forms, with good accuracy and precision.
Drugs Perphenazine Fluopromazine monohydrochloride Fluphenazine hydrochloride Electrode Electrode Amperometry

"Reduction In Size By Electrochemical Pre-treatment At High Negative Potentials Of The Background Currents Obtained At Negative Potentials At Glassy Carbon Electrodes And Its Application In The Reductive Flow Injection Amperometric Determination Of Nitrofu"
Analyst 1986 Volume 111, Issue 2 Pages 157-161
Ahmad B. Ghawji and Arnold G. Fogg

Abstract: A newly polished vitreous-carbon disc electrode (3 mm diameter) was pre-treated in 0.1 M H2SO4 at -2.7 V for 1 min to minimize reactivity towards dissolved O. A background current of only 1 µA was obtained when this electrode was held at -1.05 V in a flow injection system constructed from PTFE tubing and with use of a de-oxygenated pH 7 Britton - Robinson buffer solution as mobile phase (6.5 mL min-1). The size of the signal obtained when 100 µL of non-de-oxygenated mobile phase was injected as the sample blank was only 0.02 µA at -0.7 V. When nitrofurantoin was determined under the latter conditions, this blank signal was equivalent to ~0.2 µM-nitrofurantoin.
Nitrofurantoin Amperometry Electrode

"Determination Of Morphine By Flow Injection Analysis With Chemiluminescence Detection"
Analyst 1986 Volume 111, Issue 6 Pages 635-640
Richard W. Abbott, Alan Townshend and Richard Gill

Abstract: The sample (25 µL) is injected into a 0.1 M tetraphosphoric acid carrier stream (pH 1.2; 1.3 mL min-1) and this stream is subsequently mixed with 0.6 mM KMnO4 (1.3 mL min-1). The resulting luminescence intensity is measured in a flow cell 'viewed' by a sensitive photomultiplier tube. The sampling rate is 150 h-1. Calibration graphs are rectilinear (log. - log. scale) in the range 0.1 nM to 0.1 mM morphine, and at the 10 µM level the coefficient of variation is 1.8%. Of 35 other narcotic analgesics investigated, only compounds structurally related to morphine exhibited chemiluminescence. Various metals present in trace amounts exhibited quenching effects.
Drugs Morphine Clinical analysis Chemiluminescence Interferences Quenching

"Automated Flow Injection Spectrophotometric Determination Of Zinc Using Zincon: Applications To Analysis Of Waters, Alloys, And Insulin Formulations"
Analyst 1986 Volume 111, Issue 11 Pages 1311-1315
Michael A. Koupparis and Paraskevi I. Anagnostopoulou

Abstract: Water samples were filtered (0.45 µm membrane filter) followed by adjustment of the filtrate to pH 9 with 0.5 M borate buffer. Copper alloy samples were dissolved in concentrated HNO3 (10 ml), and the solution was diluted, neutralized with 5 M NaOH to phenolphthalein, and diluted with 0.05 M borate buffer. Insulin formulations were deproteinized with 1 M HCl (1 ml) and 0.61 M trichloroacetic acid (8 ml). After centrifugation, the supernatant solution (2 ml) was neutralized with 1 M NaOH (2 ml) and diluted to 10 mL with 0.05 M borate buffer. Aliquots (300 µL) of test solution containing <10 µg mL-1 of Zn were injected into a stream of mixed reagent (0.01 M KCN - 0.1 M ascorbic acid in borate buffer solution) at pH 9. After passing through a 150-cm mixing coil, the stream was mixed with a second reagent stream (10% cyclohexanone - aqueous 0.016% zincon in borate buffer solution) at pH 9. After reaction, the absorbance was measured at 620 nm with a detection limit of 0.05 µg mL-1 of Zn. Results were in agreement with reference values for the alloys by AAS.
Zinc Clinical analysis Spectrophotometry Method comparison Reference material

"Turbidimetric Determination Of Chlorhexidine Using Flow Injection Analysis"
Analyst 1987 Volume 112, Issue 1 Pages 87-90
J. Martinez Calatayud, P. Camp&iacute;ns Falc&oacute; and A. Sanchez Sampedro

Abstract: Thymol blue was chosen as superior to methyl orange, bromocresol green, bromocresol purple or Cu(II) for the formation of an ion-pair ppt. with chlorhexidine for turbidimetric detection at 610 nm in flow injection analysis with use of a Tecator 5020 reaction coil (138 cm x 0.5 mm). A software-driven modified simplex method was used to determine optimum analytical conditions: pH 3.4, flow rate 1.41 mL min-1, sample size 153 µL, reagent concentration. 0.41 mM. Calibration was rectilinear in the range 10.5 to 63 µg mL-1 of chlorhexidine. A 50-fold excess of ascorbic acid, aspirin and sucrose could be tolerated and benzocaine did not interfere. The method is suitable for analysis of pharmaceuticals.
Chlorhexidine Turbidimetry Interferences Optimization Simplex Tecator

"Determination Of Sulfite And Hydrogen Peroxide In Pharmaceutical Matrices Via Classical Spectrophotometry And Flow Injection"
Analyst 1987 Volume 112, Issue 6 Pages 899-902
David S. Brown and Dennis R. Jenke

Abstract: Sulfite was caused to react quantitatively at room temperature with 5,5'-dithiobis-(2-nitrobenzoic acid)(I) to form a thiol chromophore, which was determined by measuring the absorbance at 410 nm. Under similar conditions, H2O2 reacts with SO32- and can be determined indirectly. In the spectrophotometric method, the reaction rate is matrix dependent and the experimental conditions were optimized, i.e., for 50 to 600 ppm of SO32- in 0.1 mL of sample, 0.3 mL of I solution and 10 mL of the final solution containing citrate buffer (pH 6) were used to give a detection limit of 5 ppm and a precision of ~1.5%. Cationic matrix interference was controlled by the buffer. Sulfide and CN- caused a positive bias. In the flow injection method, samples (10 µL) containing 10 to 600 ppm of SO32- were introduced into a flow stream containing 80 to 320 mg L-1 of I and 0.044 M citrate buffer (pH 6). The flow injection system detected 1 ppm of SO32- with a precision of ~1.5%. The sensitivity depended on reagent flow rate. In pharmaceuticals, both methods could determine SO32- and H2O2 with high accuracy. A minor positive bias was observed in the presence of >2.5% of some amino-acids.
Sulfite Hydrogen peroxide Spectrophotometry Interferences Method comparison

"Determination Of Clonazepam By Flow Injection Analysis"
Analyst 1988 Volume 113, Issue 2 Pages 317-319
Cristina Latorre, Manuel Hern&aacute;ndez Blanco, Encarna Lorenzo Abad, Jose Vicente and Lucas Hern&aacute;ndez

Abstract: Clonazepam(I) was determined by flow injection analysis with voltammetric detection at -0.9 V with a vitreous-carbon working electrode, a Ag - AgCl reference electrode containing 3 M KCl and a Au auxiliary electrode, or with spectrophotometric detection at 308 nm. For routine work, a 50-cm reaction coil, a carrier solution of 0.1 M phosphate buffer (pH 7) containing 10% of methanol at a flow rate of 4 mL min-1 and injection volume of 200 µL for voltammetric and 250 µL for spectrophotometric detection were used. For the voltammetric method, response was rectilinear for 6.3 to 31.5 µg mL-1 of I, the detection limit was ~3.3 µg mL-1 and the coefficient of variation was 1%. For the spectrophotometric method, Beer's law was obeyed for 0.6 to 31.5 µg mL-1, the detection limit was 0.2 µg mL-1 and the coefficient of variation was 1.1%. The spectrophotometric method was applied to determine I in urine after extraction with ethyl ether. Beer's law was obeyed for 0.6 to 3.2 µg mL-1 of I and the coefficient of variation (n = 10) at the 2 µg mL-1 level was 2.5%.
Clonazepam Spectrophotometry Electrode Voltammetry

"Automated Flow Injection Spectrophotometric Non-aqueous Pseudotitrations Of Amines And Their Hydrohalide Salts"
Analyst 1988 Volume 113, Issue 5 Pages 755-760
Constantinos A. Georgiou and Michael A. Koupparis

Abstract: A sample was dissolved in anhydrous acetic acid, and the solution was injected (200 µL) into a carrier stream, for amines, of 0.2 mM HClO4 - 12 µM malachite green (C. I. Basic Green 4) in anhydrous acetic acid. The carrier for the hydrohalide salts also contained 20 mM Hg(II) acetate. The absorbance of the solution was measured at 621 nm (e = 87,900) at a flow rate of 6.3 mL min-1. The rectilinear response ranges were generally 1 to 20 mM, with detection limits between 0.09 and 0.9 mM. The coefficient of variation ranged from 0.1 to 1.6% (n = 5). In the determination of theophylline and chlorpromazine hydrochloride in two commercial formulations, results agreed well with those obtained by an official method, with coefficient of variation (n = 3 for 3 samples) of 1.9 and 1.3%, respectively.
Amines Theophylline Chlorpromazine, hydrochloride Caffeine Thiamine Procarbazine hydrochloride Spectrophotometry Method comparison Titrations

"Spectrophotometric Determination Of N-nitroso Compounds By Flow Injection Analysis"
Analyst 1988 Volume 113, Issue 8 Pages 1333-1335
Takafumi Ohta, Nozomi Goto and Shoji Takitani

Abstract: Sample solution (200 µL) is injected into a stream of ethyl acetate (0.7 mL min-1) which is then mixed with 2.5% HBr in acetic acid (0.3 mL min-1). After passing through a 2-m reaction coil the stream is mixed with 1% sulfanilamide - 0.13% N-1-naphthylethylenediammonium dichloride - 10% acetic acid (0.3 mL min-1) and passed through a 6-m reaction coil. The absorbance is then measured at 550 nm. For N-nitrosopyrrolidine(I) the calibration graph was rectilinear from 50 nM to 150 µM; for 0.1 and 5.4 µM-I, the coefficient of variation were 3.8 and 0.5%, respectively (n = 9). The sampling rate is 25 h-1. Other N-nitroso-compounds exhibited similar responses (results are tabulated). Phenol, sorbic acid and methanol did not interfere, but piperazine interfered in the determination of N-nitrosoproline. The method has been applied in the determination of nimustine hydrochloride and 1-(2-chloroethyl)-3-(methyl-α-D-glucopyranos-6-yl)-1-nitrosourea in injection solution; results agreed with those obtained by HPLC.
Drugs Nitroso compounds Nimustine hydrochloride 1-(2-chloroethyl)-3-(methyl-α-D glucopyranos-6-yl)-1-nitrosourea Spectrophotometry Interferences Method comparison

"Flow Injection Amperometric Detection Based On Ion Transfer Across A Water-solidified Nitrobenzene Interface For The Determination Of Tetracycline And Terramycin"
Analyst 1988 Volume 113, Issue 10 Pages 1541-1543
Huamin Ji and Erkang Wang

Abstract: A 0.1-g portion of a drug sample containing tetracycline(I) or oxytetracycline(II) was dissolved in 0.1 M HCl (10 ml), and the solution was diluted to 25 mL with water, then further diluted 100-fold with mobile phase. A 20 µL aliquot of solution was injected into the flow-through cell (diagram given); the mobile phase (0.5 mL min-1) was 0.1 M KH2PO4 - 1 mM EDTA of pH 2.0, and the applied potential was 0.43 V. Response was rectilinear from 2 to 200 µM-I, and from 5 to 300 µM-II; the detection limits were ~20 and 50 ng of I and II, respectively. The coefficient of variation (n = 22) for 0.2 mM I and -II were 1.2 and 2.5%, respectively. Results agreed well with those of a biological assay. Sixty samples could be analyzed in 1 h.
Drugs Tetracycline Oxytetracycline Terramycin Amperometry Solid liquid interface

"Stopped-flow Fluorimetric Determination Of Theophylline In Pharmaceutical Preparations"
Analyst 1988 Volume 113, Issue 4 Pages 559-562
Ma. Carmen Guti&eacute;rrez, Agustina G&oacute;mez-Hens and Dolores P&eacute;rez-Bendito

Abstract: The reaction of theophylline with cerium(IV) has been applied to the kinetic-fluorimetric determination of theophylline using a simple and versatile modular stopped-flow system. The method is based on the monitoring of the variation in the fluorescence intensity during the formation of a 1 : 1 compound between the oxidation product of theophylline and cerium(III). The stopped-flow technique provides the data required to determine the reaction rate from each kinetic curve in only 8 s. The linear range of the proposed method is 1-250 µg ml-1 of theophylline and the detection limit is 0.95 µg ml-1. Within- and between-assay precision data have been obtained. The stopped-flow method has been satisfactorily applied to the determination of theophylline in various pharmaceutical preparations. Analytical recoveries are in the range 95.0-102.0%. The results obtained show that the stopped-flow technique is suitable for routine pharmaceutical analysis.
Theophylline Fluorescence Stopped-flow

"Flow Injection Spectrophotometric Determination Of Selenium Based On The Catalysed Reduction Of Toluidine Blue In The Presence Of Sulfide Ion"
Analyst 1989 Volume 114, Issue 6 Pages 715-717
Carmen Martinez-Lozano, Tom&aacute;s P&eacute;rez-Ruiz, Virginia Tom&aacute;s and Concepci&oacute;n Abell&aacute;n

Abstract: A stream of 0.003% toluidine blue solution is mixed with a stream of alkaline 5 mM S2- containing 0.01 M BaNa2EDTA and 4% of formaldehyde (both 0.74 mL min-1), sample solution (80 µL) is injected into a carrier stream of aqueous 4% formaldehyde (0.74 mL min-1), and the two streams merge before passing to a 400-cm mixing coil. After 30 s, the flow stops for 30 s and the solution is pumped to a detector for absorbance measurement at 620 nm. The calibration graph is rectilinear for 0.2 to 2 µg of Se and the detection limit is 0.08 µg. The coefficient of variation (n = 11) for a 0.56 µg sample was 0.01%. The method was applied to ores and pharmaceuticals.
Selenium Spectrophotometry Catalysis Stopped-flow

"Flow Injection Method For The Assay Of Phenothiazine Neuroleptics In Pharmaceutical Preparations Using Ammonium Vanadate"
Analyst 1991 Volume 116, Issue 2 Pages 177-181
Salah M. Sultan

Abstract: Phenothiazine solution was injected into a stream of 0.4% ammonium vanadate solution in dilute H2SO4, the mixture was passed through a reaction coil (45 cm or 2 m), and the oxidized product was determined spectrophotometrically. For chlorpromazine, promethazine, trimeprazine and perphenazine, the concentration. of acid was 0.5, 1.5, 0.6 and 0.5M, respectively, and detection was at 526, 515, 510 and 525 nm, respectively. Ranges of application were 160 to 1000, 160 to 2100, 400 to 1200 and 0 to 200 ppm, respectively, with coefficient of variation (n = 7) 0.5%. Sampling rates were 129 to 150 h-1. Results showed good agreement with those of the official B.P. method.
Phenothiazine Spectrophotometry Standard method

"Photochemical - Spectrofluorimetric Determination Of Phenothiazine Compounds By Unsegmented-flow Methods"
Analyst 1991 Volume 116, Issue 2 Pages 171-176
Danhua Chen, Angel Rios, M. D. Luque de Castro and Miguel Valcarcel

Abstract: Phenothiazines were injected into carrier solution, irradiated with 254 nm radiation, and fluorescent products were detected at 373 nm (excitation at 253 nm). Stopped-flow and 'normal' flow injection methods were used. Chlorpromazine and promethazine in aqueous solution and perphenazine in 5 mM HCl were injected into 1 mM HCl, 1 mM NaOH and 1 mM HCl, respectively, as carrier solution Limits of detection were 20, 50 and 20 ng mL-1, respectively, and calibration graphs were rectilinear up to 2 to 3 µg mL-1. The coefficient of variation (n = 11) were all 2% for 1 µg mL-1 of drug. Tolerated levels of other compounds likely to be in pharmaceutical preparations are tabulated.
Chlorpromazine Promethazine Perphenazine Fluorescence Photochemistry Stopped-flow UV reactor Interferences

"Spectrophotometric Determination Of Oxytetracycline By Flow Injection"
Analyst 1991 Volume 116, Issue 2 Pages 183-186
A. A. Alwarthan, S. A. Al-Tamrah and S. M. Sultan

Abstract: Sample solution (200 µL) was injected into a stream (0.436 mL min-1) of 0.1% NH4Fe(SO4)2 in 2 mM H2SO4, which then passed through a 50-cm reaction coil. The absorbance of the mixture was measured at 435 nm. Conditions were optimized, though the flow rate was a compromise between sensitivity and sample throughput. The calibration graph was rectilinear for 10 to 80 µg mL-1. Of metals examined, only V interfered strongly; of excipients, riboflavine showed a slight interference. Recovery from standard solution was quantitative, but recoveries from pharmaceutical preparations was 103 to 112%.
Oxytetracycline Spectrophotometry Flow rate measurement Interferences Optimization Sensitivity

"Solvent Extraction - Spectrophotometric Determination Of Berberine And Benzethonium In Drugs With Tetrabromophenolphthalein Ethyl Ester By Batchwise And Flow Injection Methods"
Analyst 1991 Volume 116, Issue 2 Pages 187-190
Tadao Sakai

Abstract: The cited ethyl ester (I) reacts with the cited quaternary salts (II and III, respectively) to form blue ion asociates, which can be extracted into 1,2-dichloroethane and determined at 610 nm. The batch method was to develop a flow injection method. Thus, sample was injected into a stream (0.8 mL min-1) of water, which was mixed with 0.3 M KH2PO4 - 0.1 M Na3BO3 (pH 11) also at 0.8 mL min-1. This was mixed with 10 µM-I in 1,2-dichloroethane (0.8 mL min-1), the mixture was passed through an extraction coil (2 m x 0.5 mm) and a PTFE membrane phase separator, and the absorbance of the organic phase was measured. Calibration graphs were rectilinear for 1 to 5 µM-II and 2 to 10 µM-III. The coefficient of variation (n = 6) was 0.9% for 1 µM-II and 1.2% for 4 µM-III. Sample throughputs were 45 and 30 h-1, respectively. Some amines interfered, particularly in the batch method.
Berberine Benzethonium Spectrophotometry Sample preparation Interferences Teflon membrane Phase separator Solvent extraction

"Use Of Ion-selective Electrodes In Kinetic Flow Injection: Determination Of Phenolic And Hydrazino Drugs With 1-fluoro-2,4-dinitrobenzene Using A Fluoride-selective Electrode"
Analyst 1991 Volume 116, Issue 3 Pages 233-237
John C. Apostolakis, Constantinos A. Georgiou and Michael A. Koupparis

Abstract: A flow injection (FI) kinetic potentiometric method for the determination of phenolic (acetaminophen and isoxsuprine) and hydrazino (isoniazid) drugs is described. This work shows the usefulness of ion-selective electrodes as detectors in FI systems, not only for direct ion determination but also in routine kinetic analysis. The method is based on the reaction of 1-fluoro-2,4-dinitrobenzene (FDNB) with the analytes in a weakly alkaline medium, which proceeds through the liberation of fluoride from the reagent. The slow reactions with phenols are catalyzed by micelles of cetyltrimethylammonium bromide. The reaction rate is monitored with a fluoride-selective electrode in a wall-jet configuration and is used to construct a calibration graph of antilog(delta E/S)-1 versus c (where E = potential, s = slope of the electrode and c = concentration), using the fixed-time approach. The response time and the long-term stability of the electrode were found to be adequate for such kinetic determinations. The proposed method overcomes problems associated with end-point spectrophotometric methods using FDNB and allows measurements in highly colored or turbid solutions. The optimized method has a linear concentration range of 1 x 10^-4-50 x 10^-4 mol L-1, a measurement throughput of 20 or 40 per hour and the precision ranges from 1.8 to 3.6% relative standard deviation (n = 3). Results obtained for commercial pharmaceutical formulations compare favourably with those given by reference methods. In the flow injection method described, sample solution is injected into water (3 mL min-1), which is mixed with 4.3 mM 1-fluoro-2,4-dinitrobenzene in acidified aqueous ethanol - acetone (0.8 mL min-1) and 13 or 15 mM NaOH without or containing 0.5 mM hexadecyltrimethylammonium bromide (for hydrazino and phenolic compounds, respectively). After passage through a 100-cm reaction coil, total I and pH adjustment buffer (pH 5.5; 1.2 mL min-1) was added, and after passage through a 50-cm reaction coil, F- was detected with a selective electrode. Paracetamol and isoxsuprine were determined as phenolic drugs and isoniazid as a hydrazino drug. Calibration graphs were rectilinear for 0.1 to 5 mM, and coefficient of variation were 1.8 to 3.6% (n = 3). The sampling rate was 20 or 40 h-1. Results for pharmaceutical formulations agreed with reference methods.
Hydrazine Phenols Drugs Electrode Potentiometry Spectrophotometry Buffer Catalysis Kinetic Micelle pH

"High-pressure Flow Injection Assembly. Indirect Determination Of Glycine By Atomic Absorption Spectrometry"
Analyst 1991 Volume 116, Issue 3 Pages 327-329
J. Martinez Calatayud and J. V. Garcia Mateo

Abstract: A procedure for the determination of glycine is described. The method is based on the reaction of the analyte with finely powdered, solid copper(II) carbonate in a continuous-flow assembly. The optimum experimental conditions of pH, temperature, sample volume, flow-rate, column length and internal diameter, and the linear range of calibration, were studied. Interference from foreign substances that accompany this amino acid in pharmaceutical formulations was studied, and the method was applied to the determination of glycine. Sample solution (adjusted to pH 9.5) was injected into a carrier stream of CO32- - HCO3- buffer solution (pH 9.5), and this was passed through a packed-bed reactor (5 mm x 0.9 mm) containing solid CuCO3.Cu(OH)2.10H2O. The stream, containing the Cu - glycine complex, was passed to an AAS spectrometer for determination of Cu at 324.8 nm. The effects of pH, temperature, sample volume, flow-rate and column dimensions were investigated. The coefficient of variation was 1.9% for 50 ppm. The sampling rate was 40 h-1. The method was applied in the analysis of pharmaceuticals.
Glycine Spectrophotometry Buffer Flow rate measurement Interferences pH Reactor Temperature Indirect

"Spectrophotometric Determination Of Ascorbic Acid In Pharmaceuticals By Background Correction And Flow Injection"
Analyst 1991 Volume 116, Issue 6 Pages 641-645
Krishna K. Verma, Archana Jain, Archana Verma and Anupama Chaurasia

Abstract: Background correction has been shown to be an effective and indispensable modification in the spectrophotometric determination of ascorbic acid. The decomposition of ascorbic acid in pharmaceutical samples was carried out by incubation with sodium hydroxide to give products that were insensitive to ultraviolet light. The rapid oxidation in air of ascorbic acid, especially in dilute solutions, was avoided by the use of the flow injection principle for spectrophotometric determination and by employing a carrier stream of an anti-oxidizing nature consisting of 6 µg mL-1 of 2-mercaptoethanol in 0.25% sulfuric acid. The optimized method with a single channel manifold made use of a carrier stream flow rate of 1.1 mL min-1, an injection volume of 50 µL, a delay coil of 50 cm (0.5 mm i.d.) and detection at 245 nm. The throughput was at least 180 injections h-1. The proposed flow injection method yielded results for the analysis of 0-20 µg mL-1 of ascorbic acid that were 99-102% (relative standard deviation 0.6% or better) in agreement with those produced by comparable methods involving titration with iodine, chloranil or 2,6-dichlorophenolindophenol [4-(2,6-dichloro-4-hydroxyphenylimino)cyclohexa-2,5-dieno ne], and high performance liquid chromatography. When the agreement was not good (as low as 14% with respect to the method being compared), this was traced to the presence of substances which are known to interfere in one or other of the methods of comparison. Ascorbic acid (I) was determined in two portions of aqueous sample solution by flow injection analysis; one portion was analyzed directly and the other after treatment with 1 M NaOH to give a background correction. A portion (50 µL) of solution was injected into a carrier stream of 0.25% H2SO4 containing 6 µg mL-1 of 2-mercaptoethanol and the mixture was passed through a delay coil (50 cm x 0.5 mm) for detection at 245 nm. Recoveries of up to 20 µg mL-1 of I were 99 to 102%, with coefficient of variation of 0.6%. Results for I, in the presence of non-interfering drugs or pharmaceutical additives, agreed well with those by HPLC or titrimetry.
Ascorbic acid Spectrophotometry Interferences Method comparison

"Determination Of N-acetylcysteine In Pharmaceutical Samples By Flow Injection"
Analyst 1992 Volume 117, Issue 5 Pages 925-928
Concepcion S&aacute;nchez-pedre&ntilde;o, Ma. Isabel Albero, Ma. Soledad Garcia and Vicente Rodenas

Abstract: Aqueous solution of the samples were injected into 0.5 mM PdCl2 in 1 M HCl and the absorbance was measured at 380 nm. The calibration graph was rectilinear from 50 µM to 5 mM with a limit of detection of 10 µM. The coefficient of variation (n = 10) for 0.4 mM was 1.4%. By using the doublet-peak flow injection mode with 0.2 mM PdCl2 in which the peak width was measured the range was extended to 50 mM. The coefficient of variation for 0.5 mM was 3.4%. The results for four commercial preparations by both methods were close to certified values. Two flow injection (FI) methods, involving spectrophotometric detection, are proposed for the determination of N-acetylcysteine (NAC). Both methods are based on the formation of a yellow complex between NAC and Pd(II) in a medium of 1 mol L-1 HCl. In the first method, which is based on the conventional FI technique, NAC is determined over the range 5 x 10^-5 - 5 x 10^-3 mol L-1, and in the second, in which the doublet-peak FI mode is used, the working range is extended (5 x 10^-5 - 5 x 10^-2 mol L-1). The FI methods were applied to the determination of NAC in pharmaceutical samples.
N-acetylcysteine Spectrophotometry Doublet peaks Manifold comparison Complexation Reference material Peak width

"Spectrofluorimetric Flow Injection Method For The Individual And Successive Determination Of L-cysteine And L-cystine In Pharmaceutical And Urine Samples"
Analyst 1992 Volume 117, Issue 6 Pages 1025-1028
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Jos&eacute; Carpena

Abstract: The procedure is based on the rapid oxidation of L-cysteine (I) by Tl(III) with concomitant formation of fluorescent Tl(III). The inclusion of a selecting valve and a Cu-coated Cd column (6 cm x 3 mm) allows the successive determination of I and L-cystine. Calibration graphs were rectilinear from 5 to 50 µM and 2 to 20 µM, resectively. Results are tabulated for the analysis of pharmaceuticals and urine. Recoveries in urine were quantitative. A flow injection configuration is proposed for the determination of L-cysteine and L-cystine individually and for mixtures of both analytes. The procedure is based on the rapid oxidation of L-cysteine by thallium(III) with concomitant formation of fluorescent thallium(I). The inclusion of a selecting valve and of a copper-coated cadmium column in the configuration allows the successive determination of two analytes. Linear calibration graphs were obtained between 5 x 10^-6 and 5 x 10^-5 mol L-1 of L-cysteine and between 2 x 10^-6 and 2 x 10^-5 mol L-1 of L-cystine. The applicability of the method to the determination of L-cysteine and L-cystine in pharmaceutical preparations was demonstrated by investigating the effect of potential interferents and by the analysis of commercial preparations. The method was successfully applied to the determination of L-cysteine and L-cystine in urine samples.
Cysteine Cystine Fluorescence Simultaneous analysis Reduction column Interferences

"Simplex-optimized And Flow Injection Spectrophotometric Assay Of Tetracycline Antibiotics In Drug Formulations"
Analyst 1992 Volume 117, Issue 7 Pages 1179-1183
Salah M. Sultan, Fakhr-Eldin O. Suliman, Salih O. Duffuaa and Ideisan I. Abu-Abdoun

Abstract: The modified simplex method was applied to the optimization of experimental conditions for the determination of tetracycline, chlortetracycline, oxytetracycline and demeclocycline. For all compounds, a 157 µL sample was injected into a carrier stream containing Fe(III). The concentration. of the Fe(III) were 554, 626, 701 and 447 ppm, the flow rates were 3.72, 4.37, 3.72 and 3.72 mL min-1 and the reaction-coil lengths were 55, 85, 45 and 45 cm for the four compounds, respectively; 1 mM H2SO4 was used as the overall reaction medium. A sampling frequency of 170 h-1 was attained for all compounds, as well as a coefficient of variation of 0.9% (n = 5). The accuracy was found to be good because the Student t-values were less than the theoretical ones when the results were compared with those obtained by conventional spectrophotometry. There was no interference from excipients in dosage forms. The modified simplex method was applied to the selection of the proper experimental conditions for the flow injection spectrophotometric determination of tetracycline, chlortetracycline, oxytetracycline and demeclocycline. In the method a 157 mm3 sample volume was injected, for all the compounds, into the carrier stream of iron(III) of concentrations 554, 626, 701 and 447 ppm flowing at rates of 3.72, 4.37, 3.72 and 3.72 mL min-1, thus passing through a reaction coil of length 55, 85, 45 and 45 cm for the respective compounds, all in 0.001 mol L-1 sulfuric acid as an over-all reaction medium. A high sampling frequency of the order of at least 170 h-1 was attained for all the compounds A high precision with a relative standard deviation of less than 0.9% was also obtained. The accuracy was found to be high as the Student t-values were calculated to be less than the theoretical values when the results were compared with those obtained by the conventional spectrophotometric method. There were no interferences from excipients in dosage forms when the method was applied to pharmaceutical preparations.
Tetracycline Chlorotetracycline Oxytetracycline Demeclocycline Spectrophotometry Interferences Optimization Simplex Method comparison

"Determination Of Ascorbic Acid In Pharmaceuticals And Urine By Reverse Flow Injection"
Analyst 1992 Volume 117, Issue 10 Pages 1635-1638
Ma. Isabel Albero, Ma. Soledad Garc&iacute;a, C. S&aacute;nchez-Pedre&ntilde;o and Jos&eacute; Rodr&iacute;guez

Abstract: Pharmaceutical sample diluted to 250 mL with water and urine sample (15 ml) treated with 2 mL of 0.1 M Na2H2EDTA and diluted to 25 mL with water were analyzed by reverse flow injection based on the reaction with the EDTA - Co(III) complex in a 5% diethylamine medium with spectrophotometric detection at 540 nm. The first flow injection method used peak-height and allowed determination of ascorbic acid (I) from 0.2 to 5 mM; the second, using peak-width, allowed 2 to 50 mM I detection. Recovery of I in urine was quantitative. Effects of foreign ions are tabulated. Two reverse flow injection (FI) methods, using spectrophotometric detection, are proposed for the determination of ascorbic acid. Both methods are based on its reaction with the EDTA-Co(III) complex in a medium of 5% diethylamine. In the first method, using the peak-height FI technique, ascorbic acid is determined over the range from 2 x 10^-4 to 5 x 10^-3 mol L-1 and in the second, using the peak-width FI method, the working range is extended (2 x 10^-3-5 x 10^-2 mol L-1). Both FI methods were applied to the determination of ascorbic acid in pharmaceuticals while the peak-height FI technique was also used to determine ascorbic acid in urine.
Ascorbic acid Spectrophotometry Reverse Peak width Linear dynamic range Interferences

"Batch And Flow Injection Spectrophotometric Determination Of Aztreonam"
Analyst 1992 Volume 117, Issue 11 Pages 1789-1792
M. I. Gonz&aacute;lez Mart&iacute;n, C. Gonz&aacute;lez P&eacute;rez and M. A. Blanco L&oacute;pez

Abstract: A method for the spectrophotometric determination of aztreonam (I) operating manually and by flow injection is reported. The method is based on the reaction with hydroxylamine to form hydroxamic acid and the subsequent reaction with Fe(III), giving a red complex. The effect of reagent concentration. was studied and reaction conditions are discussed; Ni(II) was used as catalyst. The method was applied to the determination of aztreonam in pharmaceutical products.
Aztreonam Spectrophotometry Catalysis Method comparison

"Photochemical Determination Of Ascorbic Acid Using Unsegmented Flow Methods"
Analyst 1992 Volume 117, Issue 11 Pages 1761-1765
Antonio Sanz-Mart&iacute;nez, Angel R&iacute;os and Miguel Valc&aacute;rcel

Abstract: Several continuous-flow manifolds were developed to implement the photochemical reaction between ascorbic acid and methylene blue. The reaction was carried out in the reactor coil or flow cell depending on which region was irradiated. The method was applied to a variety of samples including vitamin preparations, homemade fruit juices and commercial fruit juices. The calibration graph was rectilinear from 20 to 200 µg L-1 of ascorbic acid (I). The coefficient of variation (n = 11) was 2.4% for 40 µg mL-1 of I. The max. tolerated ratios of foreign species in the determination of 5 µg mL-1 of I are tabulated. Several continuous-flow manifolds were developed in order to implement the photochem. reaction between ascorbic acid and methylene blue. Each design has special features that make it suitable for a specific application. The reaction was carried out in the reactor coil or flow cell depending on which region was irradiated. The analyte was determined at the microgram per mL level, with relative standard deviations ranging from 1.8 to 5.0%. Various types of samples were analyzed using the proposed methodology
Ascorbic acid Spectrophotometry Photochemistry Interferences

"Organic-phase Biosensors For Monitoring Phenol And Hydrogen Peroxide In Pharmaceutical Antibacterial Products"
Analyst 1993 Volume 118, Issue 3 Pages 277-280
Joseph Wang, Yuehe Lin and Liang Chen

Abstract: Organic-phase biosensors open new opportunities for assays of challenging pharmaceutical products. Such opportunities are illustrated for the rapid determination of phenol and peroxide antiseptics in different anti-infective formulations. The tyrosinase and peroxidase enzyme electrodes offer reliable quantification of these antibacterial agents following sample dissolution in the organic solvent. The dynamic properties of these enzyme electrodes are exploited for rapid and reproducible flow injection assays of the pharmaceutical products (relative standard deviation = 1.6-1.9%). Such developments should facilitate rapid quality control testing in the pharmaceutical industry and should be applicable to other therapeutic agents and products. Applicability to cosmetic products containing hydrogen peroxide is also demonstrated.
Phenol Hydrogen peroxide Electrode Sensor

"Extraction Spectrofluorimetric Method For The Determination Of Erythromycin And Its Esters In Pharmaceutical Formulations Using Manual And Flow Injection Procedures"
Analyst 1993 Volume 118, Issue 5 Pages 567-571
A. Sanz, V. Tom&aacute;s, C. Martinez-Lozano and T. P&eacute;rez-Ruiz

Abstract: A sensitive and rapid extraction-spectrofluorimetric method for the determination of erythromycin, based on the formation of an ion pair with Erythrosine B, is described. The calibration graph resulting from the measurement of the fluorescence of the chloroform extract (10 mL) at 560 nm with excitation at 544 nm is linear over the range 10-600 µg of erythromycin per 20 mL of total volume of aqueous phase, with a relative standard deviation (RSD) of 1.5% for 3.7 µg mL-1 erythromycin. The method can be successfully adapted to an unsegmented flow system, the peak height being proportional to erythromycin concentration over the range 0.65-5.88 µg of erythromycin per 400 mm3 of sample solution injected. Up to 45 samples h-1 can be processed with an RSD of 2.9-3.8%. Manual and flow injection methods were satisfactorily applied to the determination of erythromycin in pharmaceutical preparations. n the manual batch procedure, erythromycin (I) solution (0.5 mg mL-1) was mixed with 2.8 mM Erythrosine B (C. I. Acid Red 51) and 0.1 M phosphate buffer of pH 5, diluted with water, then extracted with CHCl3 with shaking for 1 min. After centrifugation, the fluorescence intensity of the CHCl3 phase was measured at 560 nm (excitation at 544 nm). For the determination of I derivatives (esters and salts), sample containing the equivalent of 50 mg of free base was dissolved in ethanol, diluted with phosphate buffer solution of pH 8 and set aside for 3 h at 60°C. After dilution with water, the above procedure for I base was followed. The calibration graph was rectilinear from 0.5 to 30 µg mL-1 of I base in the aqueous phase; the detection limit was 0.26 µg mL-1. The coefficient of variation were 2.3%. The method was successfully adapted to an unsegmented flow system (details given); the peak height was proportional to I concentration. from 0.65 to 5.88 µg of I. Up to 45 samples h-1 could be processed, with a coefficient of variation of 2.9 to 3.8%. Both manual and flow injection methods were applied successfully to the analysis of pharmaceuticals.
Erythromycin Erythromycin, esters Fluorescence Sample preparation Extraction Method comparison

"Continuous-flow Chemiluminometric Determination Of Tetracyclines In Pharmaceutical Preparations And Honey By Oxidation With N-bromosuccinimide"
Analyst 1993 Volume 118, Issue 6 Pages 633-637
Stergios A. Halvatzis, Meropi M. Timotheou-Potamia and Antony C. Calokerinos

Abstract: A continuous-flow-chemiluminometric method for determining tetracycline (I), oxytetracycline (II), doxycycline (III) and chlortetracycline (IV) and demeclocycline (V) in pharmaceutical preparations and honey is described. It is based on the chemiluminescence produced by the action of N-bromosuccinimide on tetracyclines in alkaline solution The calibration graphs were rectilinear from 0.05 to 3.0, 0.5 to 5.0, 0.5 to 7.0, 0.5 to 7.0 and 0.3 to 3.0 µg mL-1 of I, II, III, IV and V, respectively. The corresponding detection limits were 0.005, 0.4, 0.23, 0.22, 0.002 µg mL-1. Recoveries of 95.2 to 103.7 and 89.2 to 106.6% were obtained for commercial pharmaceutical preparations and honey samples, respectively. Coefficients of variation were 5% for both honey and the pharmaceuticals. There was no interference from common excipients.
Tetracycline Oxytetracycline Doxycycline Chlorotetracycline Demeclocycline Chemiluminescence Interferences

"Immobilization Of Glutamate Oxidase On Non-porous Glass Beads. Automated Flow Injection System For The Assay Of Glutamic Acid In Food Samples And Pharmaceuticals"
Analyst 1993 Volume 118, Issue 6 Pages 723-726
Constantine D. Stalikas, Miltiades I. Karayannis and Stella M. Tzouwara-Karayanni

Abstract: The assay involved the immobilization of glutamate oxidase on non-porous glass beads for the construction of single-bead string reactors (SBSR). The Trinder reaction was used for the entrapment of the H2O2 generated by the enzymatic reaction. The flow injection system consisted of a four-way pneumatically actuated injection valve, an eight-channel peristaltic pump and a filter spectrophotometer equipped with a fiber optic for the transmission of the light from the source to the flow-through cell for measurement. The sample solution containing glutamic acid (I) or glutamate was injected into the carrier stream (phosphate buffer, pH 7.8) and flowed through the SBSR with the immobilized enzyme in a 0.8-mm Teflon tube. The H2O2 was mixed with Trinder's reagent in phosphate buffer and proceeded through a second reactor with untreated glass beads. Detection was at 510 nm. The calibration graph was rectilinear from 10 to 500 µM-Iand the coefficient of variation (n = 6) was 1.8%. The detection limit was 5 µM-I. Recoveries ranged from 97 to 105%.
Glutamic acid Spectrophotometry Immobilized enzyme Glass beads Single bead string reactor

"Bioluminescent Flow-sensing Device For The Determination Of Magnesium(II)"
Analyst 1993 Volume 118, Issue 7 Pages 849-853
Stefano Girotti, Elida Ferri, Severino Ghini, Pavel Rauch, Giacomo Carrea, Roberto Bovara, Aldo Roda, Maria Antonietta Giosu&eagrave;, Piero Masotti and Gianni Gangemi

Abstract: A continuous-flow system was developed for the determination of magnesium in serum, drugs and beverages. The system used firefly luciferase (LUC) or recombinant luciferase (r-LUC) from Escherichia coli (1 mg/ml) immobilized on a nylon coil activated with triethyloxonium tetrafluoroborate, 1,6-diaminohexane and glutaraldehyde or immobilized on a column of epoxy methacrylate (Eupergit) placed inside a luminometer. The bioluminescence continuous-flow assay manifold for the nylon coil system involved two streams. The first supplied the coil with the working bioluminescent solution and the second was a continuous-flow of air into which a known volume (5-20 µL) of sample was injected. The same system was used for the Eupergit column except that the air was replaced with Tris acetate buffer. The optimal conditions were 0.05 mM luciferin and 0.3 mM ATP at a flow rate of 0.4 ml/min for an LUC-Eupergit column or an r-LUC-nylon coil; the corresponding responses were linear for 0.05-6.7 and for 0.01-6.7 mM Mg. Both the intra- and inter-assay RSD were 7%. There was no interference from Ca(II), Mn(II), Fe(II), Cu(II), Zn(II), or Co(II).
Magnesium(II) Bioluminescence Interferences

"Simultaneous Determination Of Chlorpyrifos And Carbaryl By Differential Degradation Using Diode-array Spectrophotometry Optimized By Partial Least Squares"
Analyst 1994 Volume 119, Issue 6 Pages 1183-1188
A. Espinosa-Mansilla, F. Salinas and A. Zamoro

Abstract: A 50 µL portion of a 40% ethanolic sample solution containing 12.5 nmol of chlorpyrifos (I) and carbaryl (II) was injected into a carrier stream (flow rate not given) of 0.5 M NaOH/40% ethanol/H2O2 (0.55 g/l). By using a stopped-flow system coupled with a diode-array detector, the absorption spectra of the solution were recorded from 295-380 nm at reaction times of 0, 10, 30, 45 and 55 s. Partial least squares (PLS) methods were applied to determine the optimum reaction time (~10 s) for the simultaneous determination of I and II. The optimized matrices, obtained by using PLS-1 and PLS-2 methods, were used to determine I and II in synthetic mixtures. Recoveries were quantitative. The method was also used to determine I and II in a commercial formulation.
Carbaryl Chlorpyrifos Spectrophotometry Optimization Partial least squares Stopped-flow

"Sensitive Determination Of Periodate And Tartaric Acid By Stopped-flow Chemiluminescence Spectrometry"
Analyst 1994 Volume 119, Issue 8 Pages 1819-1824
Abaji Gaikwad, Manuel Silva and Dolores P&eacute;rez-Bendito

Abstract: For the cited determination, two solutions were prepared. The first consisted of the sample solution (containing 1-250 µM-NaIO4 or 5 µM-NaIO4 and 5-50 µM-disodium tartrate at pH 5.7 for the determination of periodate and tartaric acid, respectively) in a final volume of 10 mL. The second solution consisted of 5 mL of 10 mM alkaline luminol, 0.5 mL of 1 M triethanolamine and 3 mL of 10 µg/ml Mn(II) in a final volume of 10 mL at a final pH of 11.4. The two solutions (0.04 mL of each) were placed in separate drive syringes and mixed simultaneously by injecting the syringe contents into a stopped-flow cell kept at 25°C. The chemiluminescence produced was monitored at 425 nm. For tartaric acid determination, a 30 min waiting time was employed before mixing the two solutions. The calibration graphs were linear from 1-250 µM-periodate and from 5-50 µM-tartaric acid; the corresponding detection limits were 0.12 and 1.5 µM. The RSD (n = 11) were 2%. The method was used to determine tartaric acid in pharmaceuticals.
Periodate Tartaric acid Chemiluminescence Stopped-flow

"Photokinetic Determination Of Riboflavin And Riboflavin 5'-phosphate Using Flow Injection Analysis And Chemiluminescence Detection"
Analyst 1994 Volume 119, Issue 8 Pages 1825-1828
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Antonio Sanz and Virginia Tom&aacute;s

Abstract: In a photolysis cell were placed 2 mL of 0.1 M phosphate buffer of pH 6, 1 mL of 0.1 M EDTA, 1 mL of 1.8 µM-iron(III) ammonium sulfate, 1 mL of 0.5 mM H2O2 and an appropriate volume of sample solution to yield a final riboflavin or riboflavin 5'-phosphate concentration of 0.1-5 µM. The solution was diluted to 10 mL with water and irradiated for 60 s at 25°C. A 35 µL portion of the photolysed solution was injected into a carrier stream (1.7 ml/min) of 1 M phosphate buffer of pH 12 and mixed with a reagent stream (1.7 ml/min) containing 0.1 mM luminol and 3 µM-haematin. The mixture was transported to a flow cell and the light emitted from the chemiluminescence reaction was measured. Diagrams of the photolysis cell and flow injection manifold used are given. The calibration graph was linear from 0.1-3 µM-riboflavin and riboflavin 5'-phosphate. RSD (n = 10) were 0.9-1.3%. The method was applied to animal tissues, foods and pharmaceuticals.
Chemiluminescence Kinetic Photochemistry

"Chemiluminescence Determination Of Tetracyclines Based On Their Reaction With Hydrogen Peroxide Catalysed By The Copper Ion"
Analyst 1995 Volume 120, Issue 2 Pages 463-466
X. R. Zhang, W. R. G. Baeyens, A. Van den Borre, G. Van der Weken, A. C. Calokerinos and S. G. Schulman

Abstract: A flow injection method for the determination of tetracycline (I), chlortetracycline (II) and oxytetracycline (III) is described. Sample was mixed with 2 mL 0.01 M H2O2, 10 mL 0.1 M potassium persulfate and 0.5 mL 0.1 M tetrasodium diphosphate and the mixture was diluted to 20 mL with water. A portion (50 µL) of the resulting solution was injected into a carrier stream (1 ml/min) of water and mixed with a reagent stream (1 ml/min) of 5 mM Cu(II) in 50 mM ammonium carbonate of pH 9. The chemiluminescence produced was measured. Interference by Mn was masked with EDTA. The calibration graphs were linear from 0.25-25 nmol, from 25-2500 pmol and from 0.25-25 nmol of I, II and III, respectively; the corresponding detection limits were 0.1, 0.01 and 0.1 nmol. The method was used to determine I, II and III in pharmaceuticals. Recoveries were >95%.
Chlorotetracycline Oxytetracycline Tetracycline Chemiluminescence Indirect Interferences

"Use Of The Sequential Injection Technique To Determine The Concentrations And Stoichiometries Of Trimeprazine And Perphenazine Complexed With Palladium(II) In Hydrochloric Acid"
Analyst 1995 Volume 120, Issue 2 Pages 561-563
Salah M. Sultan, Fakhr Eldin O. Suliman and Bahruddin B. Saad

Abstract: A method for determining trimeprazine (I) and perphenazine (II) is described. The determination was performed by first pumping the carrier solution (HCl buffered to pH 4.7 or 4.85 for determination of I and II, respectively) for 25 s. Then 176.4 µL of Pd(II) [5 or 2.5 mM for I and II, respectively) and 176.4 µL drug solution were sequentially aspirated into a holding coil (100 cm x 0.8 mm i.d.). By means of flow reversal (29.4 µL/s), the solutions were propelled through a reaction coil (40 cm x 0.8 mm i.d.) and the absorbance was measured at 515 and 560 nm for I and II, respectively. A diagram of the manifold used is given. The calibration graphs were linear from 50-400 and from 50-500 ppm of I and II, respectively. The method was applied to the determination of I and II in synthetic samples containing some compounds usually added to pharmaceutical preparations. The recoveries were quantitative. The method was also used to determine the reaction stoichiometry.
Perphenazine Trimeprazine Spectrophotometry Complexation Sequential injection Buffer

"Flow Injection Chemiluminometric Determination Of Citrate Based On A Photochemical Reaction"
Analyst 1995 Volume 120, Issue 2 Pages 471-475
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Otilia Val

Abstract: Sample (235 µL) was injected into a stream of 0.5 mM Fe(III) in 0.01 M H2SO4 and 0.01% poly(vinyl alcohol) and transported to a coiled photochemical reactor (250 cm x 0.5 mm i.d.). When the sample zone reached the reactor, the flow was stopped and irradiation was carried out for 60 s. The flow was then resumed and the solution was merged with a buffered luminol stream, produced by previously mixing a stream of 1 M borate buffer of pH 11 with a stream of 0.5 mM luminol. The chemiluminescence generated was measured. A diagram of the manifold used is given. The total flow rate was 12 ml/min. The calibration graph was linear from 0.2-100 µM-citrate. The RSD (n = 10) for 5.5 and 0.55 µM-citrate were 0.45% and 1.5%, respectively. The throughput was 30 samples/h. Possible interferences were investigated. The method was applied to pharmaceuticals and soft drinks. The results agreed with those obtained by an enzymatic method.
Citrate Chemiluminescence Photochemistry Stopped-flow Interferences

"Automatic Extraction-spectrofluorimetric Method For The Determination Of Imipramine In Pharmaceutical Preparations"
Analyst 1995 Volume 120, Issue 4 Pages 1103-1106
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Ciriaco Sidrach

Abstract: A flow injection method for imipramine (I) determination is described. The sample solution (100 µL) was injected into a carrier stream (1 ml/min) of 0.2 M acetate buffer of pH 5 and merged with a reagent stream (1 ml/min) of 0.5 mM Erythrosine B. The mixture passed through a reaction coil (50 cm x 0.5 mm i.d.) and subsequently reached a segmenter through which a stream of CHCl3 flowed. The whole mixture passed through an extraction coil (100 cm x 0.5 mm i.d.) and finally through a phase separator. The fluorescence intensity of the organic phase was measured at 560 nm (excitation at 544 nm). A diagram of the manifold used is given. The calibration graph was linear from 0.12-2.89 µg/ml of I with a detection limit of 0.07 µg/ml. The RSD (n = 11) for 0.56 and 2.24 µg/ml of I were 1.4 and 0.84%, respectively. Recoveries were 97-102.5%. The throughput was 45 samples/h. The method was used to determine I in pharmaceuticals. The results agreed well with those obtained by spectrophotometry.
Imipramine Fluorescence Sample preparation Extraction Phase separator Method comparison

"Flow Injection Detection Of Tetracyclines By Electrocatalytic Oxidation At A Nickel-modified Glassy Carbon Electrode"
Analyst 1995 Volume 120, Issue 5 Pages 1559-1565
W. Oungpipat, P. Southwell-Keely and P. W. Alexander

Abstract: The cited modified electrode was prepared by deposition of 0.1 mM NiSO4 on to the surface of a vitreous C electrode. The Ni-modified electrode was incorporated in a flow injection system and used to determine tetracycline (I), doxycycline (II), oxytetracycline (III) and chlortetracycline (IV). The sample solution (90 µL) was injected into a carrier stream (2 ml/min) of 0.1 M KOH and transported to a flow-through thin-layer electrochemical cell consisting of dual Ni-modified vitreous C electrodes in serial configuration. Amperometric measurements were made at +550 mV vs. Ag/AgCl and the current produced was recorded. Calibration graphs were linear from 2.5-80 mg/l of I and from 2.5-100 mg/l of II, III and IV. Detection limits were 0.03, 0.92, 0.34 and 1.81 mg/l of I, II, III and IV, respectively. RSD (n = 30) were 1.58-3.2%. Recoveries were quantitative. The method was used to determine I-IV in single-component drug formulations. The results agreed well with those obtained by HPLC.
Tetracycline Doxycycline Oxytetracycline Chlorotetracycline Amperometry Electrode Method comparison

"Flow Injection Method For The Determination Of Methotrexate With A Column-packed Oxidizing Agent"
Analyst 1996 Volume 121, Issue 2 Pages 183-188
Samy Emara, Saeid Razee, Abdel-Nasser El-Shorbagi and Tsutomu Masujima

Abstract: A portion (50 µL) of the sample was injected into a carrier stream (0.5 ml/min) of 0.04 M phosphate buffer of pH 3.5. The sample zone was passed through a column (7 cm x 4.6 mm i.d.) of cerium(IV) trihydroxyhydroperoxide (preparation described) maintained at 40°C, and the reaction product was detected fluorimetrically at 463 nm (excitation at 367 nm). The calibration graph was linear for 45.4-454 ng/ml methotrexate, the detection limit was 1.3 ng/ml and the between-day RSD (n = 5) was 1.37%. Recoveries of methotrexate were quantitative. The method was applied to methotrexate formulations (tablets and injections). The results obtained agreed with those obtained by the official method.
Methotrexate Fluorescence

"Flow Injection Fourier Transform Infrared-spectrometric Determination Of Paracetamol In Pharmaceuticals"
Analyst 1996 Volume 121, Issue 5 Pages 635-639
Zouhair Bouhsain, Salvador Garrigues and Miguel de la Guardia

Abstract: A portion (200 mg) of the powdered sample was shaken ultrasonically with 20 mL ethanol in CH2Cl2 (solvent A) for 20 min. The solution was filtered and the filtrate was made up to 25 mL. A portion (400 µL) of the resulting solution was injected into a carrier stream (0.97 ml/min) of solvent A and the FTIR spectrum was recorded. Paracetamol (I) was determined by measuring the peak-height absorbance at 1515 cm-1 corrected with the baseline at 1900 cm-1. The calibration graph was linear for 0-8 mg/ml I, the detection limit was 33 µg/ml and the RSD (n = 5) was 0.2%. The throughput was 45 samples/h. The interference from citric acid (if present as an excipient) was eliminated by using first-derivative measurements between 1518 and 1509 cm-1 for the quantification of I.
Acetaminophen Spectrophotometry Interferences

"Flow Injection Fluorometric Method For The Determination Of Ranitidine In Pharmaceutical Preparations Using O-phthalaldehyde"
Analyst 1996 Volume 121, Issue 8 Pages 1043-1046
Carmen L&oacute;pez-Erroz, Pilar Vin&atilde;s, Natalia Campillo and Manuel Hern&aacute;ndez-C&oacute;rdoba

Abstract: Powered tablets were dissolved in H2O; injectable solutions were diluted with water. After filtration, a portion (200 µL) of the resulting solution was injected into an aqueous carrier stream at a flow rate of 0.5 ml/min and merged with a stream of 5 mM sodium hypochlorite in 0.05 M acetate buffer of pH 4.5 at a flow rate of 0.5 ml/min. The mixture was passed through a 0.8 m reaction coil maintained at 25°C, and then merged with a reagent stream at a flow rate of 1 ml/min, obtained by merging a stream of 0.02 M o-phthalaldehyde in 0.5 M borate buffer of pH 10.5 (buffer A) at a flow rate of 0.5 ml/min with a stream of 0.1 M 2-mercaptoethanol in buffer A at a flow rate of 0.5 ml/min. The solution was passed through a 2.5 m reaction coil maintained at 25°C. Detection was at 450 nm (excitation at 350 nm). The calibration graph was linear from 20-500 ng/ml ranitidine; the detection limit was 13 ng/ml. RSD was 3.4% (n = 10). The recovery of ranitidine was quantitative.
Ranitidine Fluorescence

"Turbidimetric Flow Method For The Enantiomeric Discrimination Of L- And D-aspartic Acid"
Analyst 1996 Volume 121, Issue 10 Pages 1397-1400
Monika Hosse, Evaristo Ballesteros, Mercedes Gallego and Miguel Valc&aacute;rcel

Abstract: A method for L- and D-aspartic acid (L- and D-I, respectively) determination based on their inhibition of the crystallization of L- and D-histidine, respectively, is described. For L-I, sample at pH 3-10 was aspirated at 0.3 ml/min and mixed with a stream (0.3 ml/min) of L-histidine (3 g/l) and with a stream (1.3 ml/min) of propan-2-ol. The mixture was passed through an injection valve and 100 µL of the solution were injected into a carrier stream (0.7 ml/min) of propan-2-ol. The absorbance curve, reflecting the time course of crystal growth, was recorded at 550 nm. The induction period before the onset of crystallization was used to calculate the analyte concentration. For D-I the procedure was as above, except that the L-histidine solution was replaced by a 2.8 g/l D-histidine solution. Calibration graphs were linear from 3-40 and 4-40 mg/l, respectively, for L- and D-I with corresponding detection limits of 1 and 1.8 mg/l. RSD (n = 11) were 2.1-2.5%. The method was applied to pharmaceutical products.
Aspartic acid Turbidimetry

"Enzymic Determinations With Rotating Bioreactors And Continuous-flow-stopped-flow Processing. Determination Of Choline Esters In Pharmaceuticals"
Analyst 1996 Volume 121, Issue 11 Pages 1695-1698
Beatriz L&oacute;pez Ruiz, Mercedes S&aacute;nchez-Cabezudo and Horacio A. Mottola

Abstract: An enzymatic method for determining succinylcholine (suxamethonium; I) and acetylcholine (II) in pharmaceuticals is described. The sample was diluted with water and the resulting solution was pumped into a flow-through cell containing a rotating (1064 rpm) Teflon disc with cholinesterase and choline oxidase co-immobilized on the top surface of the disc (details of immobilization procedure used are given). Measurements were made by stopping the flow for 60 s. The H2O2 produced from the enzymatic reaction was detected amperometrically at a Pt ring working electrode located just above the rotating Teflon disc and held at +0.6 V vs. Ag/AgCl. The initial rate of response was measured and used for quantification of I and II. The calibration graphs were linear from 2-12 and 0.1-1.6 mM for I and II, respectively. The detection limit for I was 2.9 µM (no detection limit given for II).
Choline Acetylcholine Amperometry Stopped-flow

"Chemiluminescence Determination Of Penicillamine Via Flow Injection Applying A Quinine-cerium(IV) System"
Analyst 1996 Volume 121, Issue 11 Pages 1569-1572
Z. D. Zhang, W. R. G. Baeyens, X. R. Zhang and G. Van Der Weken

Abstract: Sample (50 µL) was injected into an aqueous carrier stream of a flow injection manifold (schematic shown) and mixed with reagent streams of 10 mM quinine in 0.1 M H2SO4 (4 ml/min) and 2 mM Ce(IV) in 0.1 M H2SO4 (4 mL/min) and the chemiluminescence intensity produced was measured. The calibration graph was linear for 2-200 µM-penicillamine (I) and the detection limit was 15 pmol. The RSD (n = 10) was M I. The method was applied to the analysis of pharmaceuticals. Recoveries of 50 µM I added to tablets were 93-101%.
Penicillamine Chemiluminescence

"Determination Of Copper(II) By Anodic-stripping Voltammetry Using A Flow-through System"
Analyst 1996 Volume 121, Issue 12 Pages 1903-1906
A. Economou and P. R. Fielden

Abstract: An automated flow system for Cu determination by anodic stripping voltammetry is described. The system (diagram given) could be operated in either flow injection (FI) or continuous-flow (CF) mode. Two types of flow-through cell, viz., a wall-jet or a thin-layer cell, were employed and Hg-plated vitreous C micro- or macro-electrodes were used as the working electrode. In the FI mode, the sample (100 µL) was injected into a carrier stream of 0.1 M HNO3 at a flow rate of 2 ml/min while the working electrode was held at -0.4 V vs. Ag/AgCl. The flow was then stopped; after a 10 s rest period, a potential scan to 0.1 V was initiated. In the CF mode, the sample was drawn at a flow rate of 1 ml/min through the working electrode held at -0.4 V. After 20 min, the cell was washed with 0.1 M HNO3. The flow was stopped and, after a 10 s rest period, the potential was scanned to 0.1 V. The FI method was applied to the analysis of tap water and pharmaceuticals; the CF method was applied to seawater analysis (results presented).
Copper Voltammetry Electrode Electrode Electrode Stopped-flow

"Chemiluminescence Determination Of Tiopronin By Flow Injection Analysis Based On Cerium(IV) Oxidation Sensitized By Quinine"
Analyst 1997 Volume 122, Issue 2 Pages 103-106
Yining Zhao, Willy R. G. Baeyens, Xinrong Zhang, Anthony C. Calokerinos, Kenichiro Nakashima and Guido Van Der Weken

Abstract: A flow injection analysis method is proposed for the determination of tiopronin based upon the oxidation by cerium(IV) in dilute sulfuric acid medium and sensitized by quinine. With the peak height as a quantitative parameter applying optimum working conditions, tiopronin is determined over the 1-400 µM range (150 µL per injection, n = 10, r = 0.9994) with a detection limit of 0.34 µM and an RSD (n = 10) less than 2% at 20 and 50 µM. The proposed method, combining the advantages of speed and sensitivity, was applied to the routine determination of tiopronin in a pharmaceutical preparation.
Tiopronin Chemiluminescence Indirect Sensitivity

"Determination Of Lignocaine Hydrochloride By Ion-pairing Flow Injection With Piezoelectric Detection"
Analyst 1997 Volume 122, Issue 2 Pages 111-113
Mo Zhihong, Luo Jie and Li Menglong

Abstract: A sample (50 µL) was injected into a carrier stream of 5 mM sodium dodecyl phenylsulfonate of pH 3 at a flow rate of 2 ml/min. The mixture was passed through a 30 cm mixing coil before piezoelectric detection with a quartz crystal microbalance. The calibration graph was linear from 0.01-2 mg/ml lignocaine hydrochloride (I); the detection limit was 8 µg/ml. RSD was 0.29% (n = 10) at the 1 mg/ml level of I. The throughput was 120 samples/h. The method was applied to pharmaceuticals. The results obtained agreed with those obtained by titrimetry. Recoveries were 99-103% I added to pharmaceuticals. A rapid and simple method for the determination of lignocaine hydrochloride by ion-pairing flow injection analysis was developed. It is based on the formation of an ion pair between lignocaine hydrochloride and sodium dodecyl phenylsulfonate and piezoelectric detection. The calibration curve was linear between 0.01 and 2.00 mg mL-1, with a detection limit of 8 µg mL-1, an RSD of 0.29% (10 replicates) and a sampling frequency of 120 h-1. The proposed method was satisfactorily applied to the determination of lignocaine hydrochloride in pharmaceutical preparations.
Lignocaine hydrochloride Sensor Microbalance Piezoelectric crystal Ion pair formation Method comparison Surfactant

"Flow Injection Fluorimetric Determination Of Ascorbic Acid Based On Its Photooxidation By Thionine Blue"
Analyst 1997 Volume 122, Issue 2 Pages 115-118
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Ciriaco Sidrach

Abstract: The photooxidation of ascorbic acid sensitized by Thionine Blue was studied. The Leucothionine Blue formed during the reaction is highly fluorescent. A flow injection method using merging zones is proposed for the determination of ascorbic acid over a concentration range from 8 x 10^-7 to 5 x 10^-5 mol L-1 with a throughout of 80 samples per h. The method was used for the simple and rapid determination of ascorbic acid in pharmaceuticals, fruit juices and soft drinks. A sample (250 µL) and 150 µL 80 µM-Thionine blue were simultaneously injected into two carrier streams (each flowing at 0.6 ml/min) of 0.2 M phosphate buffer of pH 3 then synchronously merged. The mixture was passed through a 200 cm PTFE reactor where it was irradiated for 20 s. Fluorescence intensity was then measured at 464 nm (excitation at 340 nm). A diagram of the manifold used is given. The calibration graph was linear from 0.14-8.8 µg/ml ascorbic acid. The throughput was 80 samples/h. The method was applied to pharmaceuticals, fruit juices and soft drinks. The results obtained agreed with those obtained by the standard 2,6-dichlorophenolindophenol method.
Ascorbic acid Fluorescence Redox Method comparison Standard method Buffer Merging zones

"Spectrofluorimetric Determination Of Vitamin K3 By A Solid-phase Zinc Reactor Immobilized In A Flow Injection Assembly"
Analyst 1997 Volume 122, Issue 2 Pages 139-142
I. Gil Torr&oacute;, J. V. Garc&iacute;a Mateo and J. Mart&iacute;nez Calatayud

Abstract: The spectrofluorimetric determination of vitamin K3 (menadione) using a flow injection (FI) assembly provided with a solid-phase reactor with immobilized zinc is described. The naphthohydroquinone was produced by means of two coupled steps in the FI system: hydrolysis of the sodium sulfite derivative of the menadione in a basic medium and reduction of the generated menadione in the zinc reactor in an acidic medium. The fluorescent product was monitored spectrofluorimetrically (lambda ex 325 nm; lambda em 425 nm). The calibration graph was linear over the range 0.1-18 µg mL-1 with a reproducibility of 1.6%; the limit of detection was 0.005 µg mL-1 and the sample throughput was 70 h-1. The influence of foreign compounds was studied and the procedure was applied to the determination of vitamin K3 in three different pharmaceutical formulations. A stream of menadione sodium hydrogensulfite in aqueous 90% acetonitrile at a flow rate of 3.5 mL/min was merged with a stream of 35 mM NaOH at a flow rate of 0.3 mL/min. The merged stream was then passed through a 330 cm mixing coil before being merged with a stream of 0.08 M HCl in aqueous 40% acetonitrile at a flow rate of 0.3 ml/min. After passing through a 10 cm mixing coil, 850 µL of the resultant solution was injected into a carrier stream of aqueous 90% acetonitrile at a flow rate of 3 mL/min. The mixture was applied to a column (35 cm x 1.5 mm i.d.) of Zn particles then through a 25 cm mixing coil. Fluorescence was measured at 425 nm (excitation at 325 nm). A diagram of the manifold used is given. The calibration graph was linear from 0.1-18 µg/ml vitamin K3 (determined as menadione sodium hydrogensulfite); the detection limit was 0.005 µg/ml and RSD was 1.6% (n = 32). The throughput was 70 samples/h. The method was applied to the analysis of pharmaceuticals.
Vitamin K3 Fluorescence Solid phase reagent Interferences Reduction column Reactor Column Detection limit Interferences Immobilized reagent

"Optosensor For Cinchona Alkaloids With C18 Silica Gel As A Substrate"
Analyst 1997 Volume 122, Issue 3 Pages 283-285
Zhilong Gong, Zhujun Zhang and Xiaofeng Yang

Abstract: A sample was mixed with 5 mL 0.5 M H2SO4 then diluted to 25 mL with water. A portion (2 ml) was injected into a carrier stream of 0.1 M H2SO4 at a flow rate of 1 ml/min and passed through a flow cell packed with C18 silica gel. The fluorescence intensity of the alkaloid(s) retained on the silica gel was measured at 430 nm (excitation at 346 nm) for quinine (I) and quinidine (II) and at 436 nm (excitation at 363 nm) for cinchonine (III) and cinchonidine (IV). The calibration graphs were linear from 5-20 000 ng/ml I and II and from 200-20 000 ng/ml III and IV. The detection limits were 2.3 ng/ml for I and II and 31.6 ng/ml for III and IV. RSD were 0.9% at the 20 ng/ml level of I and II, and 1.1% at the 4 µg/ml level of III and IV (n = 7). Sample throughput was 10 samples/h. The method was successfully applied to the determination of I in pharmaceuticals and soft drinks. A flow-through optosensor for cinchona alkaloids with C18 silica gel as a substrate is proposed. The sensor is developed in conjunction with a flow injection analysis system and is based on the retention of the cinchona alkaloids on a C18 column and the enhancement of their fluorescence. The analytical performance characteristics of the proposed sensor for the detection and quantification of these alkaloids were as follows: the detection limits of quinine, cinchonine, quinidine and cinchonidine were 2.3, 31.6, 2.3 and 31.6 ng mL-1, respectively, with relative standard deviations of 0.9% for quinine and quinidine (20 ng mL-1, n = 7) and 1.1% for cinchonine and cinchonidine (4.0 µg mL-1, n =7), respectively. Most of the common species did not interfere. The recommended method has been successfully tested for determination of quinine in pharmaceutical preparations and soft drinks.
Alkaloids Quinine Cinchonine Quinidine Cinchonidine Fluorescence Sensor C18 Column Detection limit Selectivity Silica gel Interferences Optosensing

"Application Of Oscillating-reaction-based Determinations To The Analysis Of Real Samples"
Analyst 1997 Volume 122, Issue 3 Pages 287-292
Rafael Jim&eacute;nez-Prieto, Manuel Silva and Dolores P&eacute;rez-Bendito

Abstract: The use of an oscillating reaction involving the H2O2/NaSCN/CuSO4 system in an alkaline medium for the continuous-flow analysis of real samples by the analyte pulse perturbation technique is described. The method involves the addition of small amounts of the analyte to the oscillating system and measuring the changes in the oscillation amplitude and/or oscillation period produced. The method was applied to the determination of vanillin (I) in food, paracetamol (II) in pharmaceuticals, and ascorbic acid (III) in orange juice and pharmaceuticals. The calibration graphs were linear from 1-40, 0.5-6 and 0.5-5 µmol I, II and III, respectively. RSD were n = 11). Sample throughput was 6-10 samples/h.
Acetaminophen Ascorbic acid Vanillin Spectrophotometry Oscillating chemical reaction Indirect

"Flow Injection Spectrophotometric Determination Of L-dopa And Carbidopa In Pharmaceutical Formulations Using A Crude Extract Of Sweet Potato Root As Enzymatic Source"
Analyst 1997 Volume 122, Issue 4 Pages 345-350
Orlando Fatibello-Filho and Iolanda da Cruz Vieira

Abstract: Sweet potato root (25 g) was extracted with 100 mL 0.1 M phosphate buffer of pH 7 (buffer A) containing 2.5 g Polyclar SB-100. The crude extract was used as a source of polyphenol oxidase (PPO) directly in the carrier solution in the cited determination. Twenty tablets were powdered and mixed; a portion was dissolved in buffer A then filtered and the filtrate was diluted. A portion (500 µL) was injected into a carrier stream of 120 iu PPO in buffer A at a flow rate of 10.01 ml/min. The mixture was then passed through a 400 cm coiled reactor maintained at 25°C. Absorbance was measured at 370 and 500 nm for carbidopa (I) and L-dopa (II), respectively. The calibration graphs were linear from 0.4-10 mM I and II. The detection limits were 0.2 and 0.15 µM for I and II, respectively. RSD was n = 6). Recoveries were 99-106% I and II. The throughput was 26 samples/h. A flow injection (FI) spectrophotometric method is proposed for the determination of L-dopa and carbidopa in pharmaceutical formulations. After selection of the extraction medium (e.g., buffer-to-tissue ratio, pH, buffer concentration, protective agents and/or stabilizers) and storage conditions, crude extract of sweet potato root [Ipomoea batatas (L.) Lam.] was used as an enzymatic source of polyphenol oxidase (Tyrosinase; catechol oxidase; EC.1.14.18.1) directly in the carrier. This enzyme catalyses the oxidation of these catecholamines to the corresponding dopaquinone. Further, dopaquinone undergoes a rapid spontaneous auto-oxidation to leucodopachrome, which is in turn oxidized to dopachrome; this last compound has a strong absorption at 480 and 360 nm for L-dopa and carbidopa, respectively. For the optimum extraction conditions found the enzyme activity of the crude extract did not vary for at least five months when stored at 4°C and decreased by only 4-5% during an 8 h working period at 25°C. The results obtained for L-dopa and carbidopa by the proposed enzymatic FI method were in close agreement with the label values (r1 = 0.9699 and r2 = 0.9999) and also with those obtained using a pharmacopeial method (r3 = 0.9675). The throughput was 26 samples h-1, and 2.30 mL of crude extract were consumed in each determination, corresponding to only 72 mg of the original sweet potato root. The detection limit (three times the signal blank/slope) was 1.5 x 10^-5 and 2.0 x 10^-5 mol L-1 for L-dopa and carbidopa, respectively; the recovery of L-dopa and carbidopa from three samples ranged from 98.6 to 106.3% of the added amount.
l-Dopa Carbidopa Spectrophotometry Detection limit Enzyme Method comparison

"Sequential Injection Analysis Technique For The Concentration, Stoichiometry And Formation Constant Studies Of Promethazine Hydrochloride Complexed With Palladium(II) In Hydrocloric Acid"
Analyst 1997 Volume 122, Issue 9 Pages 911-914
Salah M. Sultan and Nabeel I. Desai

Abstract: The sequential injection analysis (SIA) technique was successfully applied to the determination of promethazine hydrochloride in drug formulations. The chemical system is based on the complexation reaction of promethazine hydrochloride with Pd(II) in 8.0 x 10^-4 mol L-1 HCl and measurement of the absorbance at 504 nm. Promethazine was determined in the range 50-400 ppm using 1.0 x 10^-3 mol L-1 Pd(II) with an aspiration volume of 147.5 µL. The SIA technique was utilized for the determination of the concentration, stoichiometry and formation constant of the complexation reaction. The technique was found to be superior to flow injection analysis The SIA method was statistically compared with the official British Pharmacopoeia method and showed comparable accuracy, but with the advantages of selectivity, simplicity, speed and amounts of reagents consumed.
Promethazine hydrochloride Spectrophotometry Sequential injection Complexation Method comparison

"Room Temperature Phosphorescence Optosensor For Anthracyclines"
Analyst 1998 Volume 123, Issue 1 Pages 151-154
Fausto Alava-Moreno, Mar&iacute;a Jes&uacute;s Valencia-Gonz&aacute;lez and Marta Elena D&iacute;az-Garc&iacute;a

Abstract: A flow-through optosensor for anthracyclines based on the anthracycline-europium chelate room temperature phosphorescence energy transfer is proposed. The sensor was developed in conjunction with a flow injection analysis system and is based on the transient immobilization on a non-ionic resin (packed in a flow-through cell) of the anthracycline-europium chelate. The analysis performance characteristics of the proposed sensor for semi-automated analysis and control of very low levels of anthracycline were as follows: the detection limits for daunorubicin, doxorubicin and epirubicin were 9.0, 5.8 and 5.8 ng/mL, respectively, with an RSD of 1% for the determination of 0.22 mg/mL of each anthracycline (n = 10). Most of the common metal ions in biological samples did not interfere, except Fe(III), which caused serious interference and should be masked with 1,10-phenanthroline. The recommended method was successfully tested for determination of anthracyclines in clinical samples (urine and pharmaceutical preparations).
Anthracyclines Sensor Phosphorescence Interferences Solid phase detection

"Flow Injection Online Photochemical Reaction Coupled To Spectrofluorometry For The Determination Of Thiamine In Pharmaceuticals And Serum"
Analyst 1998 Volume 123, Issue 5 Pages 1017-1021
Hengwu Chen, Jingping Zhu, Xiaoxia Cao and Qiongjun Fang

Abstract: The photochemical reaction of thiamine was studied with a photochemical reactor made by coiling a knotted PTFE reactor around a low-pressure Hg lamp. Acetone, which was previously reported to be a sensitizer for the photochemical reaction that took place in situ in a flow-through cell, severely depressed the fluorescence signal of the photochemical reaction that took place online in the knotted PTFE reactor when Na sulfite was involved in the photochemical reaction. Experiments revealed that the effect of acetone on the photochem. reaction was dependent on the intensity of the irradiation. that was used to induce the photochemical reaction, and that acetone might impair the photochemically induced fluorescence if strong UV irradiation. was applied to induce the photochemical reaction and Na sulfite was used to enhance the fluorescence signal. Based on these observations, a flow injection online photochemical-spectrofluorometric method for the determination of thiamine was developed without using acetone. With the proposed method, a detection limit of 0.11 µg L-1 thiamine, a relative standard deviation of 0.36% for 11 determinations of 1 mg L-1 thiamine and a sampling frequency of 100 h-1 were achieved. The developed method was successfully applied to the determination of the thiamine content in various pharmaceutical preparations and serum.
Thiamine Fluorescence Knotted reactor UV reactor Photochemistry

"Chemiluminescence Determination Of Naltrexone Based On Potassium Permanganate Oxidation"
Analyst 1998 Volume 123, Issue 5 Pages 1053-1056
A. Campiglio

Abstract: A rapid method by chemiluminescence is described for the determination of naltrexone. The method is based on the chemiluminescence reaction with potassium permanganate in sulfuric acid medium. The optimum conditions for the chemiluminescence emission were investigated. With the integrated chemiluminescence intensity for 10 s after KMnO4 injection as a quantitative parameter, naltrexone can be determined over the concentration range 50-1000 ng mL-1 with a detection limit of 2.5 ng mL-1 and with a RSD (n = 10) of 0.9% and 0.5% at levels of 1000 and 100 ng mL-1, respectively. The method was applied to the determination of naltrexone in pharmaceutical preparations.
Naltrexone Chemiluminescence

"Solid Phase Reactors As High Stability Reagent Sources In Flow Analysis: Selective Flow Injection Spectrophotometric Determination Of Cysteine In Pharmaceutical Formulations"
Analyst 1998 Volume 123, Issue 8 Pages 1685-1689
M. Catal&aacute; Icardo, L. Lahuerta Zamora and J. Mart&iacute;nez Calatayud

Abstract: The flow injection spectrophotometric determination of cysteine was carried out using reaction with cobalt(II) ions entrapped in a polymeric filling in a packed-bed reactor; the released Co(II) complexed with the amino acid and was monitored at 360 nm. The method worked with a high repeatability, even with independent reactors, days, and solutions Selectivity of the procedure was tested with 20 different foreign compounds found in pharmaceutical formulations containing cysteine, parent amino acids included, and no serious interferences were observed The calibration graph for cysteine was linear over the range of 1-90 µg/mL with a relative standard deviation of 0.8% at 60 µg/mL. The calculated sample throughput was 90/h. The method was applied to determine the content of cysteine in pharmaceutical formulations.
Cysteine Spectrophotometry Solid phase reagent Interferences

"Flow Injection Spectrophotometric Determination Of Hydrogen Peroxide Using A Crude Extract Of Zucchini As A Source Of Peroxidase"
Analyst 1998 Volume 123, Issue 9 Pages 1809-1812
Iolanda da Cruz Vieira and Orlando Fatibello-Filho

Abstract: A flow injection (FI) spectrophotometric procedure is presented for determining H2O2 for pharmaceutical use and in swimming pool water samples. Crude extracts of several vegetables such as peach, yam, manioc, artichoke, sweet potato, turnip, horseradish and zucchini were studied as the source of peroxidase (donor: H2O2 oxidoreductase, POD; EC 1.11.1.7). Of these, a zucchini crude ext. gave highest specific activity and was used directly as the carrier solution This enzyme catalyzes the oxidation of guaiacol in the presence of H2O2 to tetraguaiacol, which shows strong absorbance at 470 nm. For the optimum extraction conditions found, the peroxidase activity in the crude ext. did not vary for at least 5 mo when stored at 4°C and decreased by only 2-3% during an 8 h working period at 25°C. The recovery of H2O2 from two samples ranged from 97.8 to 103.0% and a rectilinear calibration curve for H2O2 concentration. from 1.6 x 10^-5 to 6.6 x 10^-4 mol L-1 was obtained. A detection limit of 2.1 x 10^-6 mol L-1 and a sample throughput of 32 h-1 were attained. The relative standard deviations were <0.2% for H2O2 solutions containing 2.0 x 10^-4 and 4.0 x 10^-4 mol L-1 (n = 10) and a paired t-test showed that all results obtained for water samples using this FI procedure and permanganate titration agreed at the 95% confidence level.
Hydrogen peroxide Spectrophotometry Indirect Enzyme Optimization Method comparison

"Determination Of Cyanide By A Flow Injection Analysis-atomic Absorption Spectrometric Method"
Analyst 1998 Volume 123, Issue 10 Pages 2103-2107
A. V. L&oacute;pez G&oacute;mez and J. Mart&iacute;nez Calatayud

Abstract: A new flow injection analysis (FIA) procedure is proposed for the indirect atomic absorption spectrometric determination of cyanide. The FIA manifold is based on the insertion of the sample into a distilled water carrier, then the sample flows through a solid phase reactor filled with Ag iodide entrapped in polymeric resin beads. The calibration graph is linear over the range 0.2-6.0 mg L-1 of cyanide (correlation coefficient 0.9974), the detection limit is 0.1 mg L-1, the sample throughput is 193 h-1 and the relative standard deviation is 0.8%. The method is simple, quick and more selective than other published FIA procedures. The reproducibility obtained by using different solid phase reactors and solutions is in the range 2.2-3.1% (relative standard deviation). The method was applied to the determination of cyanide in commercial samples such as pharmaceutical formulations and industrial electrolytic baths.
Cyanide Spectrophotometry Solid phase reagent Indirect Resin Precipitation

"Photochemically Induced Fluorimetric Detection Of Tianeptine And Some Of Its Metabolites. Application To Pharmaceutical Preparation"
Analyst 1998 Volume 123, Issue 11 Pages 2267-2270
Mihaela Bulaceanu-Mac Nair, Jean-Jacques Aaron, Patrice Prognon and Georges Mahuzier

Abstract: The photochem. induced fluorescence (PIF) properties of tianeptine and some of its metabolites were investigated in acidic (pH 2.3) water-alcohol mixtures at room temperature Two PIF methods were developed, including bulk solution and flow injection analysis (FIA). Linear calibration plots were established over a concentration. range of more than one order of magnitude. Limits of detection ranged from 15 ng mL-1 for FIA-PIF to 25 ng mL-1 in bulk solution The RSDs were between 3 and 5%. The PIF methods were applied to the determination of tianeptine in a pharmaceutical preparation with recoveries varying from 96 to 106% in bulk solutions and from 98 to 106% for FIA-PIF.
Tianeptine Tianeptine, metabolites Fluorescence pH Photochemistry

"Indirect Atomic Absorption Spectrometric Determination Of Sulfonamides In Pharmaceutical Preparations And Urine By Continuous Precipitation"
J. Anal. At. Spectrom. 1988 Volume 3, Issue 5 Pages 725-729
Rosa Montero, Mercedes Gallego and Miguel Valc&aacute;rcel

Abstract: Two AAS methods are described that are based on continuous precipitation of sulfonamides with Ag+ or Cu(II) in a flow injection system (illustrated). Sample solution (100 µL) containing 10 to 100 µM-sulfonamide at pH 7.6 to 9.0 was continuously pumped into the system and mixed with carrier solution (200 µg mL-1 of Ag; 1.5 mL min-1, or 150 µg mL-1 of Cu; 3.1 mL min-1) at pH 6 to 7 in a 200-cm reaction coil. The peak due to the precipitating cation in a water blank was recorded first and then the peak due to the ppt. retained on a stainless-steel filter (pore size 0.5 to 2.0 µm) was measured. Sulfonamide concentration. was obtained from the difference between the two peaks. Response was rectilinear for 2.5 to 35 µg mL-1 of sulfonamide by either method, and detection limits were 1.2 and 1.4 µg mL-1 for the Ag and Cu methods, respectively. Recoveries from pharmaceuticals were quantitative. The coefficient of variation (n = 11) ranged from 1.5 to 3.0%. The Cu method was more selective than the Ag method, and could be used to determine sulfonamides in urine.
Sulfonamides Spectrophotometry Precipitation Indirect

"Determination Of Thiomersal In Biological Products By Liquid Chromatography With Inductively Coupled Plasma Mass-spectrometric Detection"
J. Anal. At. Spectrom. 1989 Volume 4, Issue 8 Pages 773-775
Diane S. Bushee, John R. Moody and Joan C. May

Abstract: Thiomersal (I) was determined in tetanus toxoid, influenza virus vaccine and diluents containing only I and NaCl, by HPLC - ICP-MS with the apparatus described previously (Analyst, 1988, 113, 1167). Separation was on a column of Pico Tag C18, with 60 mM ammonium acetate, containing 3% of acetonitrile and 50 ppm of 2-mercaptoethanol (pH 5.3) as mobile phase (1 mL min-1). The method was also applied in the detection of the decomposition products of I viz. methylmercury chloride, dimethylmercury chloride and mercuric chloride. Results were compared with those obtained by flow injection - ICP-MS.
Thiomersal Mass spectrometry Method comparison

"Flow Injection Analysis With Enzyme Thermistor Detector For Automated Determination Of β-lactams"
Anal. Chem. 1984 Volume 56, Issue 2 Pages 263-268
Georg Decristoforo and Bengt Danielsson

Abstract: Penicillins and cephalosporins have been determined in an automated flow injection system by measurement by thermistors of the heat produced when they pass through a packed-bed enzyme reactor (containing penicillinase) maintained at 30°C. Results are statistically no different to those obtained by HPLC; the detection limit for K phenoxymethylpenicillin is 1 µg, and coefficient of variation are ±0.8% (n = 10). Calibration graphs are rectilinear in the range 0.1 to 10 mg mL-1 for penicillins and cephalosporins. Sample capacity is 40 to 45 samples h-1
Penicillins Thermistor Voltammetry Enzyme Reactor

"Evaluation Of Dual-wavelength Spectrophotometry For Drug Level Monitoring"
Anal. Chem. 1984 Volume 56, Issue 13 Pages 2352-2354
Susumu Honda, Tadao Konishi, and Hirokazu Chiba

Abstract: Serum sulphanilamide was converted into an azo-dye by treatment with a solution of HCl, NaNO2 and sulphamic acid and coupling with N-1-naphthylethylenediamine. Detection was at 423 and 538 nm for the simple elimination mode and at 660 and 538 nm for the k-factor mode. All three modes studied (viz, simple elimination, k-factor and difference) were less subject to interference than was the single-wavelength technique, and they afforded coefficient of variation (n = 10) of <1.2%. Automation of the method based on the simple elimination and k-factor modes was achieved.
Sulfanilamide Spectrophotometry Detector

"Automated Flow Injection Phenol Red Method For Determination Of Bromide And Bromide Salts In Drugs"
Anal. Chem. 1986 Volume 58, Issue 2 Pages 322-326
Paraskevi I. Anagnostopoulou and Michael A. Koupparis

Abstract: The chloramine T - phenol red method was optimized by the simplex technique. The calibration graph was rectilinear from 1 to 10 mg l-1, with a coefficient of variation (n = 10) from 0.2 to 2.5% at the highest and lowest levels, respectively, and a detection limit of 90 µg l-1. Interference from Cl- and NaHCO3 was eliminated (up to 40 and 10 g l-1, respectively), and that of NH3 was decreased (tolerance limit 25 mg l-1). Glucose, starch, talc (each at 10 g l-1), Carbowax 4000, Mg stearate, Na dodecyl sulfate (each at 1 g l-1), and gelatin (0.5 g l-1) also do not interfere. Ions that react with Chloramine T, Br- or the Br2 produced during the reaction interfere, as do sulfonamides, isoniazid, salicylates, imipramine and propranolone hydrochlorides, and almost all organic substances with a nucleophilic substituent on the phenyl group. Interfering compounds having an acidic or basic functional group can be removed online by Amberlite XAD-2 resin. Recoveries of 2.5 to 5 mg L-1 of Br- added to seawater were from 98.6 to 103.3% and from serum samples spiked with 19.6 to 103 mg L-1 they were from 97.2 to 103%. In the analysis of eight commercial drugs, recoveries by the proposed method agreed well with those by the USP XX 1980 method. Up to 120 measurements h-1 can be performed.
Drugs Bromide Clinical analysis Spectrophotometry Amberlite Interferences Simplex

"Generation Of Chemiluminescence Upon Reaction Of Aliphatic Amines With Tris (2,2'-bypyridine) Ruthenium(III)"
Anal. Chem. 1987 Volume 59, Issue 6 Pages 865-868
James B. Noffsinger and Neil D. Danielson

Abstract: Chemiluminescence was generated from the cited reaction in a flow injection system including a 2-mm i.d. borosilicate-glass spiral T-flow cell, mounted directly opposite the photomultiplier window for detection. The carrier streams were various buffers (e.g., 10 mM Na acetate at pH 4.6 or 5.8), at a flow rate of 1 mL min-1, and the tris-(2,2'-bipyridyl)ruthenium(III) was initially produced by voltammetric oxidation of the Ru(II) complex at +1.35 V. In the pH range 4 to 6, various aliphatic amines, and some diamines and phosphines, acted as chemiluminescent reducing agents. Ranges of linearity varied from ~3 to ~5 orders of magnitude, with coefficient of variation of 2 to 8%; the lowest detection limit was 0.28 pmol for tripropylamine.
Amines, aliphatic Chemiluminescence Flowcell Tecator

"Determination Of Cysteine In Pharmaceuticals Via Liquid Chromatography With Post-column Derivatization"
Anal. Chem. 1987 Volume 59, Issue 11 Pages 1509-1512
Dennis R. Jenke and David S. Brown

Abstract: Samples (10 µL) of diluted injection solution, containing ~40 ppm of cysteine in 0.3% H3PO4, were analyzed by ion-pair HPLC on a column (10 cm x 4.6 mm) of Hypersil ODS (5 µm) with 0.1% Na octyl sulfate - 0.3% H3PO4 solution in aqueous 10% acetonitrile as mobile phase (1 mL min-1). The eluate was mixed with a stream (0.5 mL min-1) of 0.5 M Na citrate - sodium phosphate buffer (pH 7) containing 0.03% of 5,5'-dithiobis-(2-nitrobenzoic acid) and 0.025% of EDTA. After a reaction time of 40 s, detection was effected at 412 nm. The coefficient of variation (n = 3) was 0.4%. The method discriminates against cysteine-degradation products, other thiols and NaHSO3.
Cysteine HPLC Spectrophotometry Post-column derivatization

"Rapid Heterogeneous Competitive Electrochemical Immunoassay For IgG In The Picomole Range"
Anal. Chem. 1987 Volume 59, Issue 23 Pages 2786-2789
Uditha De Alwis and George S. Wilson

Abstract: The use of an immunosorbent microreactor for a competitive heterogeneous immunoassay is demonstrated. An Fab fragment of an antibody is attached covalently, largely via the -SH molety in the hinge region, to a polymeric support (Trisacryl GF-2000). An immunosorbent results which retains about 75% of the antigen binding capacity of the soluble moiety. The flow injection Immunoassay for human IgG can be carried out with ±2-3% accuracy and precision in the subpicomole range. The total time taken for the assay is 12 min and the between-assay interval is 8 min. The technique is compatible with total automation.
Electrochemical analysis Immunoassay

"Flow Injection Analysis As A Diagnostic Tool For Development And Testing Of A Penicillin Sensor"
Anal. Chem. 1988 Volume 60, Issue 13 Pages 1250-1256
Tracy D. Yerian, Gary D. Christian, and Jaromir Ruzicka

Abstract: The sensor is based on the enzymatic hydrolysis of penicillin to penicilloic acid, resulting in a pH change which is sensed optically by a colored acid - base indicator. An integrated microconduit contains a cellulose support pad with β-lactamase cross-linked with bovine serum albumin on the pad or covalently bound to the cellulose. The indicator (e.g., Merck 9582) is also covalently immobilized on the pad. Color changes are monitored in a flow injection optosensing system by using a bundle of optical fibers. Sensor stability, speed of response, sensitivity and lifetime data were obtained. The detection limit was 0.01 mM for penicillins G and V.
Penicillin G Penicillin V Sensor Spectrophotometry Cellulose Immobilized enzyme Immobilized reagent Microfluidic Tecator Optical fiber Optosensing

"Vitamin B1-sensitive Poly(vinyl Chloride) Membrane Electrode Based On Hydrophobic Tetraphenylborate Derivatives And Their Application"
Anal. Chem. 1990 Volume 62, Issue 15 Pages 1644-1648
Guo Hua Zhang, Toshihiko Imato, Yasukazu Asano, Takaaki Sonoda, Hiroshi Kobayashi, and Nobuhiko Ishibashi

Abstract: Thiamine (I)-sensitive electrodes are described based on I - tetrakis-[3,5-bis-(2-methoxyhexafluoro-2-propyl)phenyl]borate ion-pairs as the electroactive component in the sensing membrane, and 2-nitrophenyl octyl ether as plasticizer. The electrodes give a Nernstian response down to ~0.1 µM-I at pH 4, with response times of 5 to 10 s. Interference is negligible. The method was applied to a pharmaceutical solution of I in batch and flow injection systems; results showed good correlation with those of conventional HPLC.
Electrode HPLC Membrane Interferences

"Pharmaceuticals And Related Drugs"
Anal. Chem. 1991 Volume 63, Issue 12 Pages 130R-148R
R. K. Gilpin and L. A. Pachla

Abstract: A review is presented covering the period from November 1988 to October 1990 including alkaloids, antibiotics, multi-element analysis, S-, N- and O-containing compounds and vitamins and techniques used. (693 references).
Ascorbic acid HPLC Electrode Polarography Review

"Pharmaceuticals And Related Drugs"
Anal. Chem. 1993 Volume 65, Issue 12 Pages 117R-132R
R. K. Gilpin and L. A. Pachla

Abstract: A review is presented on analytical methodologies for drugs and pharmaceuticals including alkaloids, antibiotics, inorganics, N-, O- and S-containing compounds, steroids and vitamins. (700 references).
Drugs Review

"Use Of A Regenerable Immobilized Second Antibody To Determine Azidothymidine [zidovudine] In A Flow System"
Anal. Chem. 1993 Volume 65, Issue 22 Pages 3308-3312
Stacy L. Hunt, Deborah W. Manning, Jun Zhao, and Moore U. Asouzu

Abstract: A regenerable immobilized second-antibody reactor was used to measure zidovudine (I) by competitive EIA in a flow system (block diagram given). Two portions of rabbit anti-I antibodies were injected into the system, which was washed for 10 min with PBS before two portions of peroxidase-conjugated I were injected. After washing for 10 min with PBS, an O electrode (operated at -600 mV) was stabilized for 5 min, then replicate injections of 0.18 M H2O2 were made to establish the initial enzyme activity in the reactor, as indicated by an increase in pO2. Standard unlabelled I solution was injected and permitted to compete with and displace some of the labelled I. The measured response indicated the relative decrease in enzyme activity, and was inversely related to the amount of unlabelled I. Details are given of the regeneration of the reactor. By allowing 2 min for the competitive reaction, a detection limit of ~70 pM-I was achieved; the RSD was 5.5% at 75 pM and 2.4% at 3.7 nM (n = 6). The method was used to determine I in pharmaceuticals.
Azidothymidine Electrode Immobilized antibody

"Online Monitoring Of Hydrophobic Compounds At Self-assembled Monolayer Modified Amperometric Flow Detectors"
Anal. Chem. 1993 Volume 65, Issue 14 Pages 1893-1896
Joseph Wang, Hui Wu, and Lucio Angnes

Abstract: Substantial improvements in the selectivity of amperometric monitoring of flowing streams are obtained by using detectors coated with neutral n-alkanethiol monolayers. Permselective transport properties, based on solute polarity, are obtained and add a new dimension of information to amperometric detection. An elegant way of varying the transport properties of hydrophobic drugs and the exclusion of hydrophilic compounds is achieved by varying the chain length (i.e., hydrophobicity) of the n-alkanethiol modifier. The dynamic behavior of the detector is evaluated with respect to the thiol chain length or concentration, flow rate, solute concentration, and other variables. The surface coating, and hence the discriminative properties, are highly stable under the vigorous hydrodynamic conditions existing in the flow cell. Highly selective flow injection measurements of chlorpromazine in an untreated urine sample are illustrated. Copyright 1993, American Chemical Society. .
Chlorpromazine Organic compounds Hydrocarbons, aromatic Chlorpromazine Amperometry Self assembled monolayer

"Pharmaceuticals And Related Drugs"
Anal. Chem. 1995 Volume 67, Issue 12 Pages 295R-313R
R. K. Gilpin and L. A. Pachla

Abstract: Analytical methodologies for pharmaceuticals and related compounds that appeared in Analytical Abstracts or Chemical Abstracts between November 1992 and November 1994 are reviewed. The following compounds are examined: alkaloids, antibiotics, inorganics, nitrogen- and oxygen-containing compounds, proteins and peptides, steroids, sulfur, and vitamins. Some additional techniques and miscellaneous topics are also reviewed. Some recent books, reviews, and international meetings are cited. Also cited is literature on chiral drugs; automation of flow injection analysis procedures; and various aspects of chromatography that are relevant to natural, synthetic, and recombinant products, pharmaceutical development, and hardware considerations.
Drugs Review

"Sequential Determination Of D- And L-glutamic Acid By Continuous Fractional Crystallization"
Anal. Chem. 1996 Volume 68, Issue 2 Pages 322-326
Evaristo Ballesteros, Mercedes Gallego, and Miguel Valc&aacute;rcel

Abstract: Portions of standard D- and L-glutamic acid (I) solutions of pH 5-6 were introduced (0.5 ml/min) into a flow injection manifold (illustrated) and mixed with a stream of D-histidine (4 g/l; 0.4 ml/min) in a reaction coil (50 cm x 0.5 mm i.d.) and with 2-propanol (2 ml/min) in a second coil (75 cm x 0.5 mm i.d.). A 100 µL portion, was trapped in an injection valve and mixed with a 2-propanol carrier stream (1.2 ml/min) in a coil (75 cm x 0.5 mm i.d.). Samples were mixed with L-histidine for the determination of L-I. The crystallization of D- or L-histidine was recorded from turbidity measurements in an 18 µL flow-through cell and detection at 550 nm. Calibration graphs were linear from 1-40 mg/l D- and L-I and the corresponding detection limits were 0.7 and 0.6 mg/l, respectively. The determination of each isomer was highly selective and either enantiomer was tolerated at concentrations at least 20 times higher than that of the analyte. Recoveries of L-I from three pharmaceutical preparations were 94.2-104%. Recoveries of D- and L-I in a racemic mixture were ~50%.
d-Glutamic acid l-Glutamic acid Spectrophotometry Turbidimetry Precipitation Optical isomers

"Ion-chromatographic Analysis Of Inorganic And Organic Complexing Agents"
Fresenius J. Anal. Chem. 1987 Volume 328, Issue 1-2 Pages 46-50
Joachim Wei&szlig; und Gerhard H&auml;gele

Abstract: Compounds such as polyphosphates, aminopolycarboxylic acids, aminopolyphosphonic acids and polyphosphonic and polyphosphinic acids can be separated by ion chromatography on a column (25 cm x 4 mm) of HPIC-AS7 latex anion-exchange resin with HNO3 (0.03 to 0.07M) as mobile phase (0.5 mL min-1). Post-column derivatization with Fe(NO3)3 is followed by detection of the metal complexes at 330 nm. Estimated detection limits in the ppm range for these compounds can be lowered by use of a pre-concentration. column. The method is suitable for the separation and determination of polyphosphonic and polyphosphinic acids in complex mixtures such as pharmaceutical preparations and for the determination of the purity of individual components.
Carboxylic acids, aminopoly Phosphonate Phosphonic Aminopolyphosphonic acid HPIC Spectrophotometry Post-column derivatization Latex

"Flow Injection Extraction In Theory And Practice"
Fresenius J. Anal. Chem. 1988 Volume 329, Issue 6 Pages 660-662
Bo Karlberg

Abstract: Flow injection schemes involving solvent extraction are reviewed, with examples. Procedures are given for the extractions of caffeine from beverages, anionic surfactants from aqueous samples, codeine from drugs, bitterness compounds from beer, and phenol from water. The organic extractant is 2,2,4-trimethylpentane (for beer) or CHCl3 (others). A typical system is characterized by low comsumption of organic phase (0.5 to 2 mL per sample), low sample volume (20 to 200 µL) and high sample throughput (45 to 120 h-1). (9 references).
Bittering compounds Caffeine Codeine Phenol Surfactants, anionic Sample preparation Extraction Review Tecator Theory

"Flow Injection Analysis Titrations Of Sulfide, Cysteine And Thiol-containing Drugs With Chemiluminescent Detection"
Fresenius J. Anal. Chem. 1993 Volume 345, Issue 11 Pages 723-726
I. L&oacute;pez Garc&iacute;a, P. Vi&ntilde;as and J. A. Mart&iacute;nez Gil

Abstract: The method is based on lowering of the chemiluminescence produced by the reaction between ClO- and luminol; the optimum pH for both the chemiluminescence reaction and its suppression by S2- or a thiol is 11.2 and the optimum ClO- concentration. in the flow injection analysis system used is 0.4 mM. Sample solution is injected into a stream of ClO- solution, which passes through a silicone tube (8 cm x 2 mm) and merges with 5 mM luminol before entering a flow-through chemiluminescence detector; the overall flow rate is 6.5 mL min-1. The method has been applied to aqueous solution of pharmaceuticals. Calibration graphs obtained by plotting the chemiluminescence peak width at half height vs. log. analyte concentration. were rectilinear for 1 to 100 mM of S2- and 0.1 to 100 mM of cysteine, N-acetylcysteine, N-penicillamine, 2-mercaptopropionylglycine (tiopronin) and 2-thiouracil; some variation in the slopes was observed. No interference was caused by fructose, lactose, glucose, sucrose, maltose, caffeine, salicylic acid, tartrate, oxalate or starch in up to 10-fold amount over N-penicillamine.
Sulfide Cysteine Thiols Chemiluminescence Interferences Peak width Titrations

"Flow Injection Analysis Of Cationic Disinfectants In Pharmaceuticals Using Ion Associates Formed Between Sulfonaphthalein Dyes And Quinidine"
Fresenius J. Anal. Chem. 1994 Volume 349, Issue 6 Pages 475-476
T. Sakai, H. Ohta, N. Ohno and H. Sasaki

Abstract: The extraction - flow injection apparatus was as previously described (cf. Analyst, 1992, 177, 295). Sample solution (0.18 ml) were injected into a carrier steam (0.95 ml/min) of buffer of pH 7.8. The reagent solution contained 0.1 mM quinidine and 40 µM-bromochlorophenol blue in 1,2-dichloroethane and was also pumped at 0.95 ml/min. A 4 m extraction coil was used, with back-pressure tubing (2.5-5 m x 0.25 mm i.d.) to ensure good recovery (80%) of the organic phase. Absorbances of the blue ternary complex were measured at 605 nm. Calibration graphs were linear for 5-50 µM-benzethonium chloride or berberine hydrochloride (ε = 61 000). Among 12 amines tested, only sparteine, acrinol and neostigmine interfered seriously. Similar results were obtained with a reagent solution containing 50 µM-quinidine and 40 µM-bromophenol blue and a carrier of pH 6.8. The method was tested on four drug samples and gave results in good agreement with the labelled values.
Disinfectants, cationic Benzethonium Berberine hydrochloride Spectrophotometry Interferences

"Sensitive Spectrophotometric Determination Of Ascorbic-acid In Fruit Juices And Pharmaceutical Formulations Using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (br-padap)"
Fresenius J. Anal. Chem. 1997 Volume 357, Issue 8 Pages 1174-1178
S&eacute;rgio L. C. Ferreira, Marcus L. S. F. Bandeira, Valfredo A. Lemos, Hilda C. dos Santos, A. C. Spinola Costa, Djane S. de Jesus

Abstract: A simple and very sensitive method has been developed for the determination of ascorbic acid based on the oxidation of ascorbic acid to dehydroascorbic acid by iron(III), followed by a complexation of iron(II) with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol(Br-PADAP). The iron((II) complex is formed immediately, with absorption maxima at 560 and 748 nm and a molar absorptivity of 1.31 x 10(5) l mol-1 cm-1 and 5.69 x 10(4) l mol-1 cm-1, respectively. The ascorbic acid determination is possible with a linear range up to 2.4 µg mL-1, a calibration sensitivity of 0.744 mL µg-1 at 560 nm and 0.323 mL µg-1 at 748 nm, and a detection limit of 15 ng mL-1 and 44 ng mL-1, respectively. The procedure was used for the ascorbic acid determination in several fruit juices and pharmaceutical formulations. The results demonstrated a good precision (RSD < 1%) and are in agreement with those obtained with others methods. The Br-PADAP method proposed is six times more sensitive than the method using the iron(II)-1,10-phenanthroline system. 65 References
Ascorbic acid Spectrophotometry Complexation Detection limit Redox Sensitivity Method comparison

"Cyclodextrin-based Optosensor For The Determination Of Quinine"
Fresenius J. Anal. Chem. 1997 Volume 357, Issue 8 Pages 1093-1096
Zhilong Gong and Z. Zhang

Abstract: β-Cyclodextrin (β-CD) was immobilized on to silica gel (100-200 mesh) using a standard method; 20 µL was loaded into one end of a flow-cell (25 µL) and the other end was kept free. The cell was then connected into the flow system of a simple optosensing FIA manifold (diagram given). Samples of standards (2 ml) were injected via a valve and pumped through the flow system; quinine was complexed with the β-CD. The carrier solution used throughout was 0.1 M H2SO4 at a flow rate of 2 ml/min. The fluorescence of the complex on the β-CD immobilized gel was measured at 451 nm (excitation at 350 nm). Calibration graphs were linear from 3 x 10^-9 to 2 x 10^-5 M quinine. The detection limit was 0.2 ng/ml quinine; RSD was 2.1% (n = 7) for 0.05 µg/ml quinine. The method was successfully applied to the analysis of some pharmaceuticals (results tabulated); recoveries were 97-104%.
Quinine Fluorescence Sensor Detection limit Immobilized reagent Optosensing Silica gel Standard method Method comparison

"An Optosensor For Tryptophan With C18 Silica Gel As A Substrate"
Fresenius J. Anal. Chem. 1997 Volume 357, Issue 8 Pages 1097-1100
Zhilong Gong and Z. Zhang

Abstract: C18 silica gel (15 µL) was loaded into one end of a Perkin-Elmer flow cell L225 1247 (10 x 1.8 mm i.d.) and the other end was kept free. The cell was then connected into the flow system of a simple optosensing FIA manifold (diagram given). Samples or standards (2 ml) were injected into the flow system at a flow rate of 1 ml/min. The carrier solution was 0.1 M NaH2PO4/0.1 M NaOH of pH 8. tryptophan passed into the flow cell where it was retained on the gel. Fluorescence was measured using a Perkin-Elmer LS-SO instrument with excitation and emission slits set at 5 and 15 nm, respectively. Calibration graphs were linear from 0.1-50 µg/ml tryptophan; detection limit was 25 ng/ml. RSD was 2.9% (n = 7) for 10 µg/ml tryptophan. Most common species did not interfere. The method was successfully applied to the analysis of a pharmaceutical preparation containing 18 amino-acids; composition results compared favourably with those reported by the manufacturer.
Tryptophan Fluorescence Sensor Detection limit Method comparison Optosensing Selectivity C18 Silica gel Interferences

"Determination Of Procaine Hydrochloride By Ion-pairing Flow Injection Analysis With Piezoelectric Detection"
Fresenius J. Anal. Chem. 1997 Volume 358, Issue 4 Pages 556-558
Z. Mo, J. Luo, Xiaohui Long, Ziling Xia

Abstract: The method was based on the formation of an ion pair with sodium dodecyl phenylsulfonate. Sample was injected in to 5 mM sodium dodecyl phenylsulfonate as carrier (2 ml/min) and mixed in a mixing coil (30 cm; total volume = 0.2 ml) with piezoelectric detection. The FIA system has been previously described (cf. Anal. Lett., in press). The calibration graph was linear from 0.02-2 mg/ml of procaine hydrochloride (I) with a detection limit of 0.01 mg/ml. The RSD (n = 10) was 0.3% and the sampling frequency was 120/h. The method was applied to the determination of I in pharmaceuticals.
Procaine hydrochloride Microbalance Sensor Ion pair formation Surfactant

"Flow Injection Chemiluminescence Determination Of Medazepam"
Fresenius J. Anal. Chem. 1998 Volume 362, Issue 1 Pages 167-169
S. M. Sultan, Ala'ddin M. Almuaibed, A. Townshend

Abstract: A new flow injection chemiluminescence method for the assay of medazepam is explored. The method involves the use of permanganate in sulfuric acid for the oxidation of medazepam with the emission of chemiluminescence detected by a photomultiplier tube. A simplex procedure was employed for optimizing the conditions for high sensitivity detection, which were found to be 1.03 x 10^-3 mol L-1 permanganate, 0.153 mol L-1 sulfuric acid, and 3.43 mL min-1 flow rate. The linear calibration range was 3.7 x 10^-5 to 1.7 x 10^-3 mol L-1. The detection limit (3s) and the sample throughput were 1.85 x 10^-5 mol L-1 and 100 per h, respectively. The relative standard deviation for S replicate determinations of 1.9 x 10^-4 mol L-1 medazepam was 0.15%. Common excipients (starch, glucose, maltose, lactose) used in pharmaceutical preparations had no effect.
Medazepam Chemiluminescence Interferences Optimization

"Flow Injection Analysis Of Zinc And Cobalt In Beverages, Biological, Environmental, And Pharmaceutical Samples"
Fresenius J. Anal. Chem. 1998 Volume 362, Issue 7-8 Pages 571-576
S. G. Aggarwal and K. S. Patel

Abstract: A new, simple, rapid, and selective flow injection analysis (FIA) method for the spectrophotometric quantification (speciation of inorganic and organic form) of Zn and Co with NH4SCN and malachite green (MG) in the presence of surfactants (CPC and TX-100) is described. The value of apparent molar absorptivity of the Zn- and Co-complexes are 1.23 x 104 and 8.67 x 103 L mol-1 cm-1 at absorption max., 635 nm, respectively. The detection limit (amt. causing a peak height >3 s) is 15 ppb Zn and 20 ppb Co, whereas their optimum working ranges for the quant. determinations are 0.05-2.0 ppm Zn and 0.07-2.5 ppm Co in the real samples. The sample throughput of the method is 120 samples/h at the flow rate of 5.0 mL/min with RSD of <1%. The method is free from interferences of almost all ions which are commonly associated with these metals in the complex materials. The composition of the complexes and their reaction mechanism involved are discussed. The effect of FIA and anal. variables for the determination of the metals are optimized. The method was applied to the quantification of Zn and Co in beverages, biol., environmental, and pharmaceutical samples.
Zinc Cobalt Spectrophotometry Speciation pH gradient Surfactant Interferences Complexation

"Enzyme-linked Flow Injection Immunoassay Using Immobilized Secondary Antibodies"
Microchim. Acta 1988 Volume 96, Issue 1-6 Pages 207-221
Ing Huei Lee and Mark E. Meyerhoff

Abstract: A system is described in which immobilized secondary antibodies are used to separate antibody-bound from free enzyme-labelled analyte in a flowing sample solution Theophylline(I), with adenosine deaminase as labelling enzyme and sheep anti-I as first antibody, and insulin(II), with horse-radish peroxidase as labelling enzyme and guinea-pig anti-II as first antibody, are used as model analytes. The secondary antibody (a fraction of rabbit anti-sheep whole serum antiserum for I and of sheep anti-guinea-pig whole serum antiserum for II) was contained in a silicone tube (2.7 cm x 2.54 mm) and was immobilized on carbonyldi-imidazole-activated glycerol-coated controlled-pore glass beads. The buffer carrier stream was 0.05 M Tris - HCl (pH 7.5) for I and 0.05 M sodium phosphate (pH 7.0) for II. After treating the reactor with substrate (details given), the enzymatic reaction products were detected with a NH4+-selective electrode for I or spectrophotometrically at 405 nm for II. Working ranges were 0.025 µM for I and 1 to 250 µg mL-1 for II in the injected solution.
Theophylline Insulin Immunoassay Electrode Spectrophotometry Controlled pore glass Immobilized enzyme

"Fluorimetric Determination Of Diphenhydramine By Flow Injection Analysis"
Microchim. Acta 1992 Volume 106, Issue 3-6 Pages 319-325
J. Martinez Calatayud, F. J. Blasco Martinez and S. Sagrado Vives

Abstract: Diphenhydramine solution (300 µL) was injected into a carrier stream (2 mL min-1) of 100 ppm of Ce(IV) in 0.3 M H2SO4 in a single-channel flow injection manifold. The stream passed through a 225-cm PTFE reaction coil and the Ce(III) formed was determined fluorimetrically at 359 nm (excitation at 259 nm). The calibration graph was rectilinear from 0.2 to 2 ppm of diphenhydramine. The coefficient of variation was 0.7%. Sampling frequency was 80 h-1. Lactate, citrate and ethanol interfered. The method was applied to diphenhydramine in pharmaceutical preparations. A sensitive, rapid and simple flow injection analysis (FIA) for the determination of diphenhydramine was based on a fluorimetric approach. An aqueous solution of diphenhydramine was injected into a carrier-reagent stream containing Ce(IV) in dilute sulfuric acid and the fluorescence intensity of the Ce(III) produced was monitored. Chemistry, FIA and instrumental variables were optimized. Anal. features of the method are: linear range 0.2-2 ppm, precision 0.7%, sample throughput 80/h. The influence of some foreign substances which can be found in typical pharmaceutical samples containing diphenhydramine was also investigated. The diphenhydramine content of a pharmaceutical preparation was determined.
Diphenhydramine Fluorescence Indirect Redox Optimization Interferences

"Semi-automatic Determination Of Furazolidone And Furaltadone By Continuous And Stopped-flow FIA Methods"
Microchim. Acta 1993 Volume 112, Issue 1-4 Pages 31-39
Teresa Galeano D&iacute;az, Leticia L&oacute;pez-Mart&iacute;nez, and Francisco Salinas

Abstract: Furazolidone (I) and furaltadone (II) were determined by continuous and stopped-flow FIA procedures based on the alkaline hydrolysis of these compounds to produce colored products. Sample solution in 0.5 M NaCl with 1% DMF was injected into a stream of 0.5 M NaOH with 1% DMF and the absorbance was monitored at 420 nm for I and at 423 nm for II. For the stopped-flow procedure, the flow was stopped at 30 s (for I) or 25 s (for II) after injection for a 20 s period. The calibration graphs were linear for 1-30 µg/ml of both compounds and the detection limits were 0.2-0.27 µg/ml. The RSD (n = 11) for 10 µg/ml of I and II were 1.1-2.0%. The procedures were applied to the analysis of pharmaceuticals.
Furazolidone Furaltadone Spectrophotometry Stopped-flow

"Flow Injection Spectrophotometric Determination Of Molybdenum And Vanadium With Carminic Acid In The Presence Of Cetyltrimethylammonium Bromide"
Microchim. Acta 1995 Volume 118, Issue 3-4 Pages 203-211
Tom&aacute;s P&eacute;rez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Concepti&oacute;n Paredes

Abstract: Portions (85 µL) of 4 mM carminic acid solution of ~ pH 4 were injected into streams (1.2 ml/min) of Mo or V [V was pre-reduced to V(IV) with 1% ascorbic acid] solutions. The resulting stream was merged with a stream (1.2 ml/min) of 4 mM cetyltrimethylammonium bromide, and then with a stream (1.2 ml/min) of 0.5 M acetate buffer of pH 4.6. After passing through a reaction coil (100 cm x 0.5 mm i.d.) where the flow was stopped for 60 s, the solution passed to a 18 µL flow cell for measurement of absorbance at 585 and 575 nm for Mo and V, respectively. The calibration graphs were linear for 0.76-28.8 and 0.3-9.1 µg/ml Mo and V, respectively, and the corresponding detection limits were 0.33 and 0.16 µg/ml; the corresponding RSD were 0.68-0.82% and 1.1-1.4% (n = 10). Sample throughput was 33/h. Tolerance levels of interfering ions are tabulated. The method was applied to steel, pharmaceuticals (multivitamins) and petroleum products (sample preparations described).
Molybdenum Vanadium Spectrophotometry Sample preparation Stopped-flow Interferences

"Biocatalysis And Biorecognition In Nonaqueous Media. Some Perspectives In Analytical Biochemistry"
Microchim. Acta 1995 Volume 120, Issue 1-4 Pages 231-242
Lorenzo Braco

Abstract: A review is presented. The basic principles and advantages of non-aqueous enzymology are outlined and its analytical applications are discussed with reference to batch analysis in organic media, flow injection enzyme reactors operating in organic media, organic-phase enzyme electrodes and enzyme-based gas-phase biosensors. Analytical applications of antibodies and abzymes in non-aqueous media are discussed and the potential of molecular imprinting techniques to generate specific recognition systems is considered. (56 references). Biocatalysis and, to a lesser extent, biorecognition in non-aqueous media (including organic solvents as well as supercritical fluids and gases) constitute at present an exciting research area which has already demonstrated its biotechnological potential in numerous, varied applications. Less attention, however, has been paid to its analytical possibilities, even though many advantages have been postulated and a wide range of poorly water-soluble analytes are present in samples (or waste materials) from food and drink, petrochemical, pharmaceutical, military and other industries. The main approaches, developed in recent years to exploit the use of enzymes, antibodies or antibody mimics in water-restricted environments for analytical purposes, as well as possible future directions are briefly discussed.
Sensor Immobilized enzyme Reverse micelle Review Catalysis

"Acetylacetone-formaldehyde Reagent For The Spectrophotometric Determination Of Some Sulfur Drugs In Pure And Dosage Forms"
Microchim. Acta 1996 Volume 124, Issue 3-4 Pages 227-233
Alaa S. Amin and Mohsen M. Zareh

Abstract: A new simple and sensitive spectrophotometric procedure for the determination of sulfacetamide sodium (I), sulfadiazine (II), sulfadimidine (III) and sulfathiazole (IV) is based on the reaction of the drug with acetylacetone-formaldehyde reagent to give a yellow product having lambda(max) at 400 nm. Optimization of the reaction conditions has been investigated. A linear correlation was obtained between absorbance at lambda(max) and the concentration. The Beer's law limits of I, II, III and IV are 4-80, 4-72, 4-60 and 4-80 µg/ml, respectively. For more accurate results, Ringbom optimum concentration ranges were evaluated to be 6-76, 8-66, 6-56 and 8-75 µg/ml for I, II, III and IV, respectively. The molar absorptivities and Sandell sensitivities for all sulfur drugs under consideration were evaluated. Relative standard deviations of 0.98, 1.07, 0.86 and 0.79% were obtained for I, II, III and IV, respectively. The method has been compared to the official method and found to be simple, accurate (t-test) and reproducible (F-test). The developed procedures were applied for bulk sulfa drugs and some of their dosage forms without interferences from additive and common prescribed drugs.
Drugs Sulfacetamide Sulfadiazine Sulfadimidine Sulfathiazole Spectrophotometry Optimization Standard method Interferences

"FIA Fluorimetric Assembly For The Determination Of Noradrenaline Hydrochloride By A Solid-phase Reactor With Immobilized Hexacyanoferrate(III)"
Microchim. Acta 1997 Volume 126, Issue 1-2 Pages 69-72
Salome Laredo Ortiz, Gustavo A. Rivas and Jos&eacute; Mart&iacute;nez Calatayud

Abstract: A portion (155.3 µL) of noradrenaline hydrochloride (I) in 0.1 M HCl was injected into a flow (1.59 ml/min) of 1.5 M NaOH, which passed through a solid-phase reactor (10 cm x 1.5 mm i.d.) packed with Duolite A102D resin-immobilized hexacyanoferrate(III), then through a PTFE tube (185 cm x 0.8 mm i.d.) prior to fluorimetric detection at 512 nm (excitation at 397 nm). The analysis was carried out at 55°C. The calibration graph was linear from 0.5-75 mg/l I, the RSD (n = 17) at 25 mg/l was 0.88% and the sample throughput was 84/h. The relative errors in determinations caused by different amounts of interferents are reported. Recoveries and detection limits are not given. An FIA assembly provided with immobilized hexacyanoferrate(III) is proposed for the fluorimetric determination of noradrenaline hydrochloride. The oxidative reagent is immobilized by means of a strong anion-exchange resin. The FIA manifold is very simple and the calibration graph is linear over the range 0.5-75 mg L-1 noradrenaline hydrochloride with an r.s.d of 0.88% (17 replicates) and a sample throughput of 84 h-1. Foreign compounds such as NaCl, sucrose, lactose and sodium sulfate caused no significant errors. The procedure is applied to the determination of noradrenaline in a medicinal formulation. (13 References)
Noradrenaline hydrochloride Fluorescence Immobilized reagent Interferences Resin Heated reaction

"FIA Fluorimetric Determination Of Adrenaline In Pharmaceutical Formulations By Oxidation With Molecular Oxygen"
Microchim. Acta 1998 Volume 128, Issue 3-4 Pages 187-190
A. C&aacute;noves Torres, A. Mellado Romero and J. Mart&iacute;nez Calatayud

Abstract: The fluorimetric determination of adrenaline is carried out in a continuous-flow assembly and by the mol. dissolved oxygen. The sample solution merges with an NaOH stream, then the resulting mixture is heated at 73°C and led to the flow-cell of the fluorimeter. The flow-assembly is very simple and the procedure is quick (107 samples h-1) reproducible (RSD 0.6%), selective, and suitable to be applied to determination of adrenaline in formulations. Calibrations graph are linear over the ranges 0.05-15 and 20-40 mg/L.
Adrenaline Fluorescence Heated reaction

"Flow Injection Determination Of Diesters As Ferric Hydroxamate Complexes"
Microchim. Acta 1998 Volume 130, Issue 1-2 Pages 81-87
Patricia A. Gallagher, Tonja J. Guianen, Paula J. Pike and Neil D. Danielson

Abstract: Diesters such as succinylcholine chloride (SCC) and dioctyl sulfosuccinate (DOSS) can be converted to hydroxamic acids which react with Fe3+ in MeOH to form a purple chelate complex having an useful absorption band at 520 nm with a molar absorptivity of ~171 L/(mol cm) and a detection limit of 1.5.cntdot.10-4 M. To adapt this method for flow injection, a MeOH/H2O solvent and acidification of the sample were required to reduce the large blank peak. The reproducibility of the flow injection method was a factor of 2 better than standard spectrophotometry but the detection limit of the former method was 2 times higher. This colorimetric method can permit anal. of pharmaceutical products containing either SCC or DOSS. Phosphatidylcholine (lecithin) can also be determined using this method.
Succinylcholine chloride Dioctylsulfosuccinate Phosphatidylcholine Spectrophotometry Complexation Method comparison

"Flow Injection Fluorimetric Determination Of Tiopronin In Pharmaceutical Preparations"
Microchem. J. 1991 Volume 44, Issue 1 Pages 72-77
Tom&aacute;s P&eacute;rez-Ruiz*, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Gabriel Lambertos

Abstract: The method described is based on the inhibition by tiopronin (I) of the oxidation of thiamine to thiochrome by Hg(II). A three-channel manifold (diagram given) is used, in which sample and 1 mM Hg(II) (pH 4) reagent streams (1.7 mL min-1) are merged and mixed in a 1-m mixing coil. The resulting stream is merged with a 0.2 M phosphate buffer stream (1.7 mL min-1) and passed to a second mixing coil (2 m). Flow is stopped for 1 min, 30 s after injection to allow the reaction to occur in the second mixing coil. Fluorimetric detection was at 445 nm (excitation at 365 nm). The calibration graph was rectilinear from 10 to 80 µM-I and coefficient of variation of 1.2%. The method was applied to dosage forms containing I.
Tiopronin Fluorescence Buffer

"Flow Injection Fluorimetric Determination Of Novalgin In Pharmaceutical Preparations"
Microchem. J. 1993 Volume 47, Issue 3 Pages 296-301
Perezruiz T., Martinezlozano C., Tomas V. and Carpena J.

Abstract: Aqueous sample solution (240 µL) was injected into a stream (1.2 mL min-1) of 0.1 mM Ce(IV) in 0.5 M H2SO4 and the mixture was passed through a reaction coil (60 cm x 0.5 mm) before fluorimetric detection at 360 nm (excitation at 260 nm). The calibration graph was rectilinear for 0.5 to 4 µg mL-1 of dipyrone. The coefficient of variation (n = 10) for 3 and 0.1 µM dipyrone were 2.8 and 0.93%, respectively; recoveries were 96.7%. The method was used to determine dipyrone in pharmaceuticals; paracetamol was found to interfere.
Novalgin Fluorescence Interferences

"Indirect Determination Of Levamisole By AAS And Precipitation In A Continuous-flow Assembly"
Microchem. J. 1993 Volume 48, Issue 1 Pages 112-117
Ortiz S. L., Mateo J. G. and Calatayud J. M.

Abstract: Reagent solution (1.9 g of HgI2 in 100 mL of water and sufficient 0.1 M KI to ensure dissolution of the solid) was injected into a carrier stream of aqueous sample solution The ppt. obtained was dissolved in a stream of ethanol and the liberated mercuric ions were monitored at 253.7 nm in an AAS system. A diagram of the manifold used is given. The calibration graph was rectilinear for 5-40 ppm of levamisole hydrochloride (I); the detection limit was 0.5 ppm. The RSD was 1.9% (n = 19) for determination of 20 ppm of I and sample throughput was 37.5/h. The method was used to determine I in pharmaceuticals.
Levamisole hydrochloride Spectrophotometry Indirect Precipitation

"Online Determination Of Perphenazine Using Flow Injection Analysis"
Microchem. J. 1993 Volume 48, Issue 3 Pages 343-348
Sultan S. M. and Abdennabi A. M.

Abstract: An accurate specific flow injection spectrophotometric method for the determination of perphenazine in the range 50-250 ppm is introduced. In the method, 110 µL of the drug is injected through a stream of 0.2% (w/v) potassium dichromate in 0.25 M sulfuric acid flowing on line as a carrier stream. The drug is oxidized on the flow to the red monocation radical, the peak absorbance of which is monitored at 525 nm. A throughput of up to 300 samples per hour is attained. The mechanism of the reaction is suggested and the method is compared with the United States Pharmacopeia method.
Perphenazine

"Application Of Photochemical Inhibition To The Fluorimetric Determination Of Nitroprusside In A Flow Injection System"
Microchem. J. 1995 Volume 52, Issue 1 Pages 33-40
Perezruiz T., Martinezlozano C., Tomas V. and Val O.

Abstract: Sample was mixed with 60 µM-phloxin (tetrachlorotetrabromofluorescein) in 0.1 M phosphate buffer of pH 6 and portions (185 µL) were injected into a stream (1.5 ml/min) of 0.1 M EDTA adjusted to pH 6 with 0.2 M NaOH. The sample and reagent streams were deaerated with Ar. The sample plug passed to a reactor coil (200 cm x 0.5 mm i.d.) where it was stopped and irradiated for 30 s using a halogen lamp. Optical fibers guided the light from the lamp to a 100 cm length of the reactor coiled around a glass tube (1 cm diameter) and placed over a mirror. The fluorescence was measured at 543 nm (excitation at 530 nm). The calibration graph was linear for 6-70 µM-sodium nitroprusside and the detection limit was 0.29 µg/ml. The RSD (n = 10) at 5 µg/ml was 1.18%. Catecholamines interfered. The method was applied to a pharmaceutical preparation with recoveries of 99.3-101.8%; the results agreed well with those obtained by polarography. The method was also applied to thiosalicylic acid-treated human serum with recoveries of 98.8-101.7%.
Nitroprusside Fluorescence Photochemistry Method comparison Interferences Optical fiber

"New Developments In Flow Injection Vapor Generation Atomic Absorption Spectrometry"
Microchem. J. 1996 Volume 53, Issue 1 Pages 42-53
Fang Zhaolun a, Tao Guanhonga, Xu Shukuna, Liu Xuezhua and Wang Jingb

Abstract: A review is presented of the enhancements in sensitivity and selectivity brought about by new developments in flow injection techniques for combined FI-vapor generation AAS. In particular, selectivity enhancements by (i) optimization of FI parameters and reaction conditions, (ii) online separation of interferents and (iii) online sample matrix modification as well as sensitivity enhancements by (i) reagent addition, (ii) online coprecipitation pre-concentration and (iii) in situ pre-concentration of hydrides in a graphite furnace are discussed in detail. The enhancements are illustrated by applications in the trace or ultratrace determination of Ge, Se, As, Sb, Bi, Sn and Pb in environmental materials and Chinese herbal medicines. (28 references).
Trace elements Spectrophotometry Interferences Review Coprecipitation Optimization Preconcentration Ultratrace

"Simultaneous Determination Of Hydrochlorothiazide And Spironolactone In Pharmaceutical Preparations Using Batch And Dynamic Systems"
Microchem. J. 1997 Volume 56, Issue 2 Pages 207-215
E. Mart&iacute;n, O. Hern&aacute;ndez, J. J. Arias and A. I. Jim&eacute;nez

Abstract: A batch and flow injection method for the determination of hydrochlorothiazide (I) and spironolactone (II) in pharmaceuticals are described. For the batch method, samples were prepared in a 20% ethanolic solution containing acetic acid/sodium acetate buffer of pH 5 and scanned from 220-350 nm. For the flow injection method, samples diluted in ethanol were injected into a carrier stream of acetic acid/sodium acetate buffer of pH 5 in 90% ethanol. Spectra were recorded from 220-350 nm at 1 s intervals and an integration time of 0.4 s. Errors were Results by numerical and graphical methods were satisfactory but the best results were achieved with multiwavelength linear regression particularly with the flow injection system.
Spironolactone Hydrochlorothiazide Spectrophotometry Method comparison Multivariate calibration Buffer Simultaneous analysis

"Sequential Injection Method For The Determination Of Oxprenolol In Pharmaceutical Products Using Chemometric Methods Of Optimization"
Microchem. J. 1997 Volume 57, Issue 3 Pages 320-327
Fakhr Eldin O. Suliman and Salah M. Sultan

Abstract: A sequential injection (SI) spectrophotometric method for the determination of oxprenolol in pharmaceutical products was developed. The method is based on the oxidation of oxprenolol online with Ce(IV) in sulfuric acid medium and the subsequent monitoring of the absorbance of the oxidized form of the drug at 480 nm. The procedure was optimized by the orthogonal array design at two and four levels. The factors included in the optimization were Ce(IV) concentration, sulfuric acid concentration, and the stop time of the composite zone at the reaction coil. The optimized SI system with a linear dynamic range of 50-400 ppm was found to be suitable for the assay of oxprenolol in pharmaceutical products.
Oxprenolol Spectrophotometry Sequential injection Optimization Chemometrics Redox Linear dynamic range

"Measurement Of Protein Using Flow Injection Analysis With Bicinchoninic Acid"
Anal. Biochem. 1987 Volume 161, Issue 1 Pages 152-156
Lawrence C. Davis* and Gary A. Radke

Abstract: The bicinchoninic acid reagent developed by Pierce Chemical Co. was used in the determination of proteins in a flow injection analyzer comprising ~8 ft of PTFE tubing (0.5 mm i.d.) with a peristaltic pump, a controlled-temperature water bath (reaction temperature was 72°C), and a spectrophotometer with flow cell. The sensitivity was comparable with that of the Lowry method. Results were obtained in <1 min at a rate of up to 60 h-1. Sample size was 5 to 20 µL and the response was rectilinear up to 10 µg of protein. We have used the bicinchoninic acid reagent developed by Pierce Chemical Co. to measure proteins in a simple flow injection analyzer. The sensitivity is comparable to that of the Lowry method and no pipetting of reagents is needed. Results are obtained in less than 1 min and samples may be run at a rate of 60/h. The response is linear over a range of protein concentration (0-10 µg) and sample size (5-20 µL) convenient for most analytical requirements. A peristaltic pump, a controlled-temperature water bath, and a spectrophotometer with flow cuvette are the only special apparatus required.
Proteins Spectrophotometry Heated reaction Method comparison

"Amperometric Determination Of Isoniazid In A Flowing Stream At The Glassy Carbon Electrode"
Anal. Lett. 1983 Volume 16, Issue 12 Pages 913-924
Mumtaz H. Shah; James T. Stewart

Abstract: The detector incorporated a vitreous-carbon electrode (area 5 mm2), an auxiliary platinum electrode and a silver - AgCl reference electrode. Acetonitrile - aqueous 0.1 M LiClO4 (9:1) was pumped (at 1 mL min-1) through the electrochemical cell (Bioanalytical Systems Model TL-5A; Kel-F), samples (<50 µL) containing isoniazid were injected into the flow, and the current was measured at +825 mV. The calibration graph was rectilinear over the range 0.05 to 6 µg mL-1 of isoniazid, and the detection limit was 0.5 ng. Sources of interference, which are relatively few, are reported.
Isoniazid Amperometry Electrode Interferences Detection limit

"Photometric Flow Injection Determination Of Psychotropic Drugs: Brotizolam And Midazolam"
Anal. Lett. 1988 Volume 21, Issue 7 Pages 1211-1220
Gallo, B.;Alonso, R.M.;Vicente, F.;Vire, J.C.;Patriarche, G.J.

Abstract: A single-channel flow injection system was used with a Gilson Minipuls-2 pump, a low-pressure Rheodyne 5020 injection valve, and a Hellma flow-through spectrophotometric cell (18 µL). The carrier solution was 0.05 M phosphate buffer (pH 7) that contained 2.2 or 5% of methanol for determination of brotizolam and midazolam, respectively. Optimum experimental conditions were: flow rate 5 mL min-1, delay coil length 40 cm and internal diameter 0.71 mm, and sample volume 75 µL. Calibration graphs were rectilinear for 1.3 µM to 0.1 mM brotizolam and 1.5 µM to 0.1 mM midazolam. The method was successfully applied to both drugs in their pharmaceutical formulations.
Brotizolam Midazolam Spectrophotometry Optimization

"Dimethyldioctadecylammonium Chloride Bilayer Membrane Vesicle-enhanced And Manganese(II)-catalysed Chemiluminescence For Determination Of Adrenaline By A Flow Injection Method"
Anal. Lett. 1989 Volume 22, Issue 11&12 Pages 2445-2461
Matsue, K.;Yamada, M.;Suzuki, T.;Hobo, T.

Abstract: A batch and a flow injection system were used to measure the chemiluminescence produced when adrenaline (I) was oxidized by dissolved O in alkaline medium. In the optimized flow system, the carrier comprised aqueous 0.1 mM Mn(II) as catalyst, and after injection the stream was merged with aqueous 0.7 M NaOH and then with 3 mM dimethyldioctadecylammonium chloride to form bilayer membrane vesicles. The log. calibration graph was rectilinear from 10 nM to 0.1 mM I, and the coefficient of variation was 0.9% at 0.5 µM (n = 5). The sampling rate was 100 h-1. A sensitivity of 1 nM was attainable by the batch method, but the reproducibility was poor. The selectivity was good for I relative to catecholamines and their metabolites, but proteins and inorganic salts interfered seriously. The method is suitable for application to pharmaceutical formulations and, with appropriate sample pre-treatment, to urine.
Adrenaline Chemiluminescence Method comparison Optimization Interferences

"Determination Of Amitriptyline With Bromocresol Purple And Flow Injection Analysis"
Anal. Lett. 1990 Volume 23, Issue 8 Pages 1371-1383
Martinez Calatayud, J.;Martinez Pastor, C.

Abstract: Bromocresol purple gave the best ppt. for the flow injection turbidimetric determination of amitriptyline. The different chemical and flow injection variables were optimized by the univariate method in a continuous-flow procedure. The calibration graph was rectilinear from 30 to 200 ppm of amitriptyline hydrochloride, the coefficient of variation (n = 20) was 1.4% and the injection rate was 39 samples h-1. Dextrose, glutamic acid, sucrose and lactose interfered. The procedure requires no liquid extraction, and was used as a control method in pharmaceutical analysis.
Amitriptyline Turbidimetry Optimization Calibration Interferences

"Spectrophotometric And Fluorimetric Determination Of 9-aminoacridine By Flow Injection Analysis"
Anal. Lett. 1990 Volume 23, Issue 12 Pages 2315-2326
Martinez Calatayud, J.;Sanchez Sampedro, A.;Villar Civera, P.;Gomez Benito, C.

Abstract: The spectrophotometric and fluorimetric determination of 9-amino acridine is carried out by means of the FIA procedures and on the basis of its own color or fluorescence. The methanol used as a carrier stream resulted in a significative increase in sensitivity and sample throughout. The method is applied to the drug determination in pharmaceutical formulations. Sample solution was injected into a carrier stream of water for spectrometric and fluorimetric detection or methanol for coulometric detection at 455 mm (excitation at 432 mm). Methanol used as carrier stream resulted in a significant increase in sensitivity and sample throughput. Tolerance levels of various foreign compounds are discussed. The method was applied in the elimination of the cited drug in various pharmaceutical formulations.
9-Aminoacridine Spectrophotometry Fluorescence Coulometry Sensitivity Organic solvent Interferences

"Photochemical Derivatization And Fluorimetric Determination Of Promethazine In A FIA Assembly"
Anal. Lett. 1992 Volume 25, Issue 7 Pages 1289-1308
Mellado Romero, A.;Gomez Benito, C.;Martinez Calatayud, J.

Abstract: Sample solution was injected into a carrier stream of water (or methanol for formulations which are not soluble in H2O) and irradiated at 254 nm as it flowed through a PTFE tube helically coiled around a mercury lamp, followed by fluorimetric detection. The modified simplex method was used to optimize the flow injection parameters, after a pre-optimization of the chemical and irradiation parameters by means of the univariate method. The calibration graph was rectilinear from 0.05 to 20 ppm of promethazine (I). The coefficient of variation (n = 24) was 1.7% for 5 ppm of I. The injection rate was 54 samples h-1. A list of the errors produced by a number of excipients is reported. The method has been applied to the determination (by aqueous extract) of a number of pharmaceutical preparations, the results obtained compared well with certified values. The flow injection fluorimetric determination of promethazine was carried out by online photoderivatization. The PTFE tubing was helically coiled around the lamp. An anal. procedure is proposed by using aqueous solution as carrier stream; the calibration graph is linear over the range 0.05-20 ppm. The influence of foreign compounds was studied and the method was applied to promethazine determination in pharmaceutical formulations.
Promethazine Fluorescence Photochemistry Reference material Simplex Optimization

"Immobilization Of Hexacyanoferrate(III) For A Flow Injection - Spectrophotometric Determination Of Promazine"
Anal. Lett. 1993 Volume 26, Issue 3 Pages 593-604
Kojlo, A.;Puzanowska Tarasiewicz, H.;Martinez Calatayud, J.

Abstract: The flow injection assembly was a single channel manifold with sample injection into a carrier stream, a reaction column and a spectrophotometer (Spekol-10, Carl Zeiss, Jena). The oxidation column (25 cm x 1 mm) was prepared by introducing K3Fe(CN)6 solution into the column packed with Amberlite IRA 400, followed by washing the column with water for 30 min. Samples of promazine HCl (I) in 0.8 M NaCl (250 µL) were injected into the carrier solution of 1 M HCl, passed through the column at a flow rate of 2 mL min-1 and the absorbance of the eluate was measured at 513 nm. The calibration graph was rectilinear from 2.5 to 25 ppm of I. Phenol (3 ppm), Na2SO3 (5 ppm), glucose (50 ppm), formaldehyde (20 ppm) and Na2EDTA (27 ppm) did not interfere. The method was suitable for the determination of I in pharmaceutical preparations.
Promazine Spectrophotometry Immobilized reagent Interferences Amberlite Oxidation column

"Fluorigenic Derivatization Of Oxazepam. Application To Its Determination In Pharmaceuticals"
Anal. Lett. 1994 Volume 27, Issue 7 Pages 1295-1306
Berrueta, L.A.;Lajusticia, L.F.;Gallo, B.;Vicente, F.

Abstract: The fluorescence reaction of oxazepam in mixtures of acetic acid and methanol and its use as a fluorescence detection system were studied. The best excitation and emission wavelengths were 364 and 469 nm, respectively. A reaction time of 5 min, a heating temperature of 100°C and a methanol/acetic acid ratio of 7:25 were the optimum conditions. The calibration graph was linear from 0.025-50 µg/ml of oxazepam and the detection limit was 0.014 µg/ml. Intra-day RSD (n = 6) was 4.25-4.13%. An FIA analytical method was developed (details given). The calibration graph for the FIA method was linear from 0.1-100 µg/ml and the detection limit was 0.035 µg/ml. The within-day reproducibility RSD (n = 3) was 5 and 0.2% for 0.5 and 50 µg/ml, respectively. The static and FIA methods were applied to the determination of oxazepam in five commercial pharmaceutical formulations (details given). HPLC was used as a reference method.
Oxazepam Fluorescence HPLC

"New Poly(vinyl Chloride) Matrix Membrane Electrode For Manual And Flow Injection Determination Of Pilocarpine In Some Pharmaceutical Preparations"
Anal. Lett. 1994 Volume 27, Issue 10 Pages 1863-1874
Elnemma, E.M.

Abstract: Solutions of 10 mM pilocarpine hydrochloride (I) and 10 mM ammonium reineckate were mixed, the 1:1 complex was dried and ground. The ion-pair was added to PVC in THF and tributylphosphate, poured into a petri dish and the solvent evaporated at room temperature. The modified PVC membrane electrode was pre-conditioned in 10 mM I for 2 days. Potentiometric measurements were made with a double junction Ag/AgCl as reference electrode. The modified PVC electrode exhibited a fast response for 0.1 M 40 µM-pilocarpine (II) at pH 4-6.5 and the detection limit was 12 µM-II. Interference from basic nitrogenous compounds and some inorganic cations was negligible. The electrode was not selective for I over some other alkaloids such as quinine, narcotine and cinchonine. The average recovery of samples containing 14.7-2.447 mg/ml of II by direct potentiometric determination was 98.2% with an RSD (n = 3) of ±0.6%. With sodium tetraphenylborate the average recovery 98.9% with an RSD (n = 3) of ±0.3%. The membrane was incorporated in a sandwich flow injection cell (details given) for measurements of 24 µg/l to 2.4 mg/ml of II. The average recovery was 99% and RSD were ±0.3%.
Pilocarpine hydrochloride Electrode Potentiometry Interferences

"FIA-fluorimetric Determination Of Adrenaline By Oxidation With A Solid-phase Reactor Of Manganese Dioxide Incorporated In Polyester Resin Beads"
Anal. Lett. 1995 Volume 28, Issue 2 Pages 239-247
Kojlo, A.;Martinez Calatayud, J.

Abstract: Samples were injected into a carrier stream (1.75 ml/min) of water which passed through a solid-phase reactor (45 cm x 1.2 mm i.d.) containing MnO2 (cf. Lahuerta Zamora et al., Anal. Chim. Acta., 1992, 263, 81) before merging with a stream (0.79 ml/min) of aqueous 1.5 M NaOH/0.5 mM ascorbic acid and passing through a mixing coil (55 cm x 0.8 mm i.d.). The oxidized adrenaline was determined fluorimetrically at 540 nm (excitation at 330 nm). The calibration graph was linear from 0.5-20 µg/ml of adrenaline and the detection limit was 0.4 µg/ml. The RSD was 2% and sample throughput was 65/h. Interferences by foreign compounds are tabulated. The method was applied to a pharmaceutical formulation.
Adrenaline Fluorescence Interferences Solid phase reagent Resin

"A Novel Strategy For Preparation Of Solid-phase Reactors. Fluorimetric Determination Of Emetine Hydrochloride"
Anal. Lett. 1995 Volume 28, Issue 6 Pages 971-978
Laredo Ortiz, S.;Martinez Calatayud, J.

Abstract: Emetine (I) was determined by measuring its fluorescence at 458 nm (excitation at 350 nm) after oxidation by I2. A solid-phase reactor was constructed by passing aqueous I2 solution through PTFE tubing for 120 min. The reagent became impregnated in the inner wall of the tubing. The reactor was incorporated in to a flow injection manifold (illustrated). water was used as carrier (4.2 ml/min). The modified simplex method was used for optimization of the flow injection parameters. A 40 cm column (1.3 mm i.d.), a sample volume of 670 µL and flow rate of 3 ml/min were optimal. The calibration graph was linear for 0.1-100 µg/ml I and the RSD was 1.3%. No detection limit is given. Sample throughput was 75/h. Details of interferences are given. The method was applied to I injection solutions. Samples (2.5 ml) were mixed with 5 mL phosphate buffer of pH 6.31 and diluted to 100 mL with H2O.
Emetine Fluorescence Solid phase reagent Simplex Optimization Interferences

"Micellar Effect Upon The Lucigenin Chemiluminescent Reaction System With Isoprenaline"
Anal. Lett. 1996 Volume 29, Issue 9 Pages 1589-1602
Alwarthan, A.A.;Al Lohedan, H.A.;Issa, Z.A.

Abstract: The effect of various surfactants, viz., hexadecyltrimethylammonium hydroxide, hexadecyltrimethylammonium bromide, sodium laurylsulfate and Brij-35 on the chemiluminescence reaction of isoprenaline (I) was studied. I was injected (50 ml) into a carrier solution containing the surfactant and NaOH (2.4 ml/min) and merged with a lucigenin stream (2.4 ml/min) at a PTFE T-piece. The resulting chemiluminescence was detected by a photomultiplier tube (schematic of the FIA manifold is given). With the cationic and anionic micellar surfactants, the chemiluminescence was lowered but the non-ionic micelles of Brij-35 enhanced the chemiluminescence. A method was developed using Brij-35 for the determination of I in pharmaceutical preparations with a detection limit of 0.05 µM.
Isoprenaline Chemiluminescence Micelle

"Indirect Catalytic Spectrophotometric Determination Of Metamizol Following Oxidation By Lead Dioxide Immobilized In A Polyester Resin Bed"
Anal. Lett. 1996 Volume 29, Issue 15 Pages 2667-2678
J. A. Garc&iacute;a Bautista; L. Lahuerta Zamora; J. Garc&iacute;a Mateo; J. Mart&iacute;nez Calatayud

Abstract: A spectrophotometric-indirect procedure for the determination of metamizol is described. The method is based on the reaction of the drug in a solid-phase (lead dioxide immobilized in a polyester resin bed) in acidic media (perchloric acid 0.01 M as carrier). The lead dioxide reactor provides simultaneously an effective oxidation of the drug and a controlled liberation of Pb(II) which acts as catalyst on the reaction pyrogallol red-potassium persulfate; the oxidation of the red pyrogallol results in a less colored solution. The decreased red color (negative FIA peaks) is monitored at 520 nm. The calibration graph is linear in the interval 2-16 ppm in metamizol. The relative standard deviation for the determination of 10.4 ppm of metamizol is 2.9% (n = 23) and the sample throughput is 72 h-1. A schematic of the FIA manifold is given. Metamizol (dipyrone; I) solution containing 50 ppm of the drug in 0.01 M HClO4 as carrier (905 µL) was injected (4 ml/min). The method is based on the reaction of the drug on lead dioxide immobilized on a polyester resin (A1-100; 20 g). The effect of the lead dioxide reactor (35 cm x 1.5 mm i.d.) was to oxidize the drug and produce a controlled release of Pb(II) which in turn catalyses the reaction with 0.1 M potassium persulfate and 0.2 mM pyrogallol red of pH 8.6 (1.4 ml/min). The result of the oxidation of red pyrogallol is to produce a less colored solution (red) which was monitored at 520 nm. The calibration graph was linear from 2-16 ppm I. The RSD (n = 25) at the 10.4 ppm I level was 2.9%. The sampling rate was 72/h. The effects of interferents were determined. The method was applied to the determination of I in two pharmaceutical formulations.
Drugs Metamizol Spectrophotometry Catalysis Solid phase reagent Immobilized enzyme Resin Interferences Indirect

"Flow Injection Analysis Of Norepinephrine Bitartrate By Ion Association With Anionic Surfactant Using A Piezoelectric Detector"
Anal. Lett. 1997 Volume 30, Issue 4 Pages 663-671
Mo Zhihong; Zhang Minjuan; Li Menglong; Xia Zhiling

Abstract: A portion (50 µL) of commercially available formulations, or spiked samples of norepinephrine bitartrate (10 mg/ml), were injected on to a 300 mm mixing coil with sodium dodecyl phenyl sulfonate or sodium dodecyl sulfonate solution (details given) at a flow rate of 2 ml/min. The resultant mixture was passed into a PTFE cell and levels of norepinephrine bitartrate were detected by piezoelectric quartz crystal and silver electrodes. The calibration graph was linear from 0.01-1.2 mg/l; the detection limit was 5 µg/ml. RSD was 0.18% (n=10). Levels of norepinephrine bitartrate in pharmaceutical preparations and recoveries are reported. The merits of the method are discussed.
Norepinephrine bitartrate Sensor Microbalance Surfactant Ion pair formation

"Stopped-flow Spectrophotometric Determination Of Dopamine And Methyldopa With Sodium Hydroxide"
Anal. Lett. 1997 Volume 30, Issue 6 Pages 1109-1120
Juan J. Berzas; Jos&eacute; M. Lemus; Prado Buitrago

Abstract: Sample (350 µL) was injected into a water carrier stream and merged with 0.6 M NaOH (0.6 ml/min) at 60°C. A schematic diagram of the stopped-flow manifold is given. The resulting solution passed into a reactor (1 m x 0.5 mm i.d.) and the solution passed into a flow cell (1.25 ml/min). Thirty seconds after the sample injection, the pump was stopped manually and the variation of the absorbance at 360 nm was monitored throughout the reaction. Calibration graphs were linear up to 0.2 mM dopamine and 0.3 mM methyldopa, respectively. The corresponding detection limits were 3.5 µM and 0.43 µM. The method was applied to the determination of the catecholamines in pharmaceutical formulations.
Methyl dopa Dopamine Catecholamines Spectrophotometry Stopped-flow Heated reaction

"Indirect Potentiometric Determination Of Chlorpromazine With An Oxidative Column In A Flow Injection System"
Anal. Lett. 1997 Volume 30, Issue 13 Pages 2353-2363
Anatol Kojlo

Abstract: A flow injection method is proposed for the determination of chlorpromazine and other N-substituted phenothiazines. The procedure is based on the oxidation of analyte with lead dioxide entrapped into polymeric material in a packed-bed reactor. The oxidation of the drug yields soluble Pb-2+, which is monitored by means of the lead ion selective electrode in the wall-jet configuration. The calibration graph is linear over the range of 0.01-2 µg mL-1 of chlorpromazine with relative standard deviation of 1.4% and sample throughput 20 h-1. The developed method was applied to the determination of chlorpromazine in pharmaceutical preparations.
Chlorpromazine Potentiometry Electrode Solid phase reagent Oxidation column Indirect

"Batch And Flow Injection Fluorimetric Determination Of Fluoxetine"
Anal. Lett. 1997 Volume 30, Issue 14 Pages 2493-2502
Gonzalez Martin, M.I.;Gonzalez Perez, C.

Abstract: A method for the fluorimetric determination of fluoxetine in continuous and discontinuous systems is reported. The method is based on the hydrolysis of fluoxetine in acid medium. The fluorescent product has a spectrum with excitation and emission maxima at 253 and 306 nm respectively. The method was applied to the determination of fluoxetine in pharmaceutical products.
Fluoxetine Fluorescence Batch injection analysis

"Application Of Flow Injection Method For The Determination Of Thioridazine"
Anal. Lett. 1997 Volume 30, Issue 15 Pages 2733-2742
A. Kojlo; E. Wolyniec; H. Puzanowska - Tarasiewicz

Abstract: A simple flow injection spectrophotometric method for the determination of thioridazine is described. The method is based on the oxidation of thioridazine with phosphotungstic acid in hydrochloric acidic media. Concentrations of thioridazine in the range 10 - 60 ppm are determined with a relative standard deviation of 1.1%. The method was applied to the determination of thioridazine in pharmaceutical formulations.
Thioridazine Spectrophotometry Redox

"Flow Injection Spectrophotometric Determination Of Amino Acids By Using 1,2-naphthoquinone-4-sulfonate Immobilized On An Ion Exchange Resin"
Anal. Lett. 1998 Volume 31, Issue 2 Pages 313-331
M. Vela; J. Saurina; S. Hern&aacute;ndez-Cassou

Abstract: A spectrophotometric flow injection method based on the immobilization of 1,2-naphthoquinone-4-sulfonate reagent in an anion-exchange Amberlite IRA 904 packed reactor is proposed for the determination of amino acids. The reagent was attached on this solid bed by electrostatic binding between the sulfonate and the ammonium quaternary groups. This solid phase reactor was used as a source of reagent since it could be desorbed by a HCl solution The reagent liberated to the flow system reacts with the amino acids in a thermostated reaction coil to give the corresponding derivatives The spectrophotometric detection was performed at 480 nm. For glycine, the response was linear up to 1.5 x 10^-3 M, the detection limit was 5.3 x 10^-4 M, the repeatability 0.4% and the reproducibility 5.4%. The method was applied to the anal. of some amino acids in several pharmaceutical samples. Results obtained were in good agreement with those from the standard method for amino acid anal.
Amino Acids Glycine Spectrophotometry Amberlite Immobilized reagent Method comparison

"Spectrofluorimetric Determination Of Iproniazid And Isoniazid In A FIA System Provided With A Solid Phase Reactor"
Anal. Lett. 1998 Volume 31, Issue 7 Pages 1209-1218
J. A. Garc&iacute;a Bautista; J. V. Garc&iacute;a Mateo; J. Mart&iacute;nez Calatayud

Abstract: A single-channel flow injection analysis (FIA) assembly is proposed for the fluorimetric determination of iproniazid and isoniazid. The oxidation of both drugs was carried out by H2O2. The excess of reagent was destroyed and removed from the flow injection manifold by a metallic copper reactor which acted as a catalyst in the decomposition of H2O2 and a degaser. The calibration graphs were linear up to 14 µg iproniazid/mL and 10 µg isoniazid/mL and the respectively. limits of detection were 0.008 and 0.005 µg/mL. The sample throughput was 24 h-1 for both drugs. The influence of interfering compounds was evaluated and the procedure was applied to the determination of iproniazid and isoniazid in pharmaceutical formulations.
Isoniazid Iproniazid Fluorescence Interferences Reduction column

"Flow Injection Spectrophotometric Determination Of Oxalate, Citrate And Tartrate Based On Photochemical Reactions"
Anal. Lett. 1998 Volume 31, Issue 8 Pages 1413-1427
Tom&aacute;s P&eacute;rez-Ruiz; Carmen Mart&iacute;nez Lozano; Virginia Tom&aacute;s; Antonio Sanz

Abstract: A flow injection configuration for the spectrophotometric determination of oxalate, citrate and tartrate is proposed. The procedure is based on the photochem. decomposition of the complexes formed between iron(III) and these anions. The iron(II) produced in the photochem. reactions was detected by measuring the absorbance after complexation with ferrozine (λmax=562 nm). Linear calibration graphs were obtained over the concentration. ranges 5.0 x 10^-6 - 1.0 x 10^-4 M, 8 x 10^-6 - 1.8 x 10^-4 M and 1.0 x 10^-6 - 2 x 10^-5 M for oxalate, citrate and tartrate, respectively. The relative standard deviations at the 1 x 10^-5 M concentration. level were within the range 1.29 - 1.47%. The sampling frequency was about 40 samples/h. The usefulness of the method was tested in the determination of oxalate in urine and spinach, of citrate in pharmaceuticals and soft drinks and of tartrate in pharmaceuticals. For the determination of oxalate in urine samples a prior separation of the analyte by precipitation with calcium chloride is recommended.
Oxalate Citrate Tartrate ion Spectrophotometry Photochemistry Complexation

"Flow Injection Chemiluminescence Determination Of Etamsylate With Electrogenerated Hypochlorite"
Anal. Lett. 1998 Volume 31, Issue 11 Pages 1917-1928
Chengxiao Zhang; Jiachu Huang; Manliang Feng; Zhujun Zhang

Abstract: A fast and simple method for the determination of etamsylate is described. The method uses chemiluminescence intensity quenching in the luminol-hypochlorite system with electrogenerated unstable reagent in a flow injection setup. The system anal. response was linear in the etamsylate concentrations range of 1 x 10^-9 to 8 x 10^-9 g/mL. The detection limit was 6 x 10^-10 g/mL. The relative standard deviation was 3.1% at 2 x 10^-9 g/mL. The method is suitable for automated and continuous anal. and was tested for determination of etamsylate in pharmaceutical formulations.
Etamsylate Chemiluminescence Electrochemical reagent generation Indirect Quenching

"Flow Monitoring Of Glutamate And Aspartate In Foods And Pharmaceutical Products With Immobilized Bienzyme Electrochemical Cells"
Electroanalysis 1992 Volume 4, Issue 9 Pages 851-857
G. Palleschi*, M. G. Lavagnini, D. Compagnone, P. Bertocchi, D. Moscone

Abstract: Electrochemical thin-layer and wall-jet amperometric cells incorporating an Immobilon-AV immunoaffinity membrane on which L-glutamate oxidase and aspartate aminotransferase were covalently co-immobilized were used in continuous-flow and flow injection analysis. The flow-through system gave higher sensitivity and the flow injection system gave better reproducibility and faster response. The wall-jet cell was the more suitable for flow injection analysis. The flow injection technique was used to determine glutamate (I) in foods and aspartate (II) in pharmaceuticals. The calibration graphs were rectilinear for 1 to 500 and 10 to 500 µmM of I and II, respectively; corresponding detection limits were 1 and 5 µM. Results correlated well with those obtained by HPLC. Electrochemical enzyme cells for glutamate and aspartate anal. have been assembled and used in continuous-flow and in flow injection analysis. The enzymes, glutamate oxidase (GOD) and aspartate amino-transferase (AST), were co-immobilized on an Immobilon Immuno-affinity membrane, which was placed into a three-electrode, flow-through cell. Additional protective membranes were used to reduce the electrochemical interferences and to protect the immobilized enzymes. Thin-layer and wall-jet cells were used and compared. Calibration curves for glutamate and aspartate showed a linearity range of 1-500 µmol/L and 10^-500 µmol/L respectively. The sensitivity was higher using the flow-through system with a response time of 2 min. Better reproducibility was achieved using the FIA procedure with a response time of less than 1 min. Glutamate in food and aspartate in some pharmaceutical products were determined Results were compared and correlated well with an HPLC procedure.
Glutamate Aspartate Electrode Method comparison Immobilized enzyme Interferences

"Sequential Flow Injection Potentiometric Determination Of Iodide And Iodine In Povidone-iodine Pharmaceuticals"
Electroanalysis 1993 Volume 5, Issue 9-10 Pages 855-861
Saad S. M. Hassan, Sayed A. M. Marzouk

Abstract: A solution of PVC, tris-(4,7-diphenyl-1,10-phenanthroline)iron(II) di-iodide complex (ionophore) and 2-nitrophenyl phenyl ether (plasticizing mediator) in THF was incorporated in a flow-through sandwich potentiometric cell (Hassan and Ahmed, J. AOAC, 1991, 74, 900). The sensor displayed a fast response (10-30 s) for 0.006-100 mM iodide over the pH range 1-11; the detection limit was 0.5 µg/ml. To determine iodide and iodine in povidone-iodine pharmaceuticals, sample solution was injected into a sodium sulfate/ascorbic acid stream followed by injection into a second stream of alkaline resorcinol. The iodine concentration. was calculated from twice the difference between the first and the second signal, and the iodide concentration. was obtained from twice the second signal less the first signal. For pharmaceuticals containing 1.1-9.1 mg/ml of iodine and 1.2-7.2 mg/ml of iodide, the mean standard deviations were 0.07 and 0.06 mg/ml, respectively (n = 3).
Iodide Iodine Potentiometry

"The Effect Of The Nature Of The Polymer Backbone On The Stability And The Analytical Response Of Polymer-modified Electrodes"
Electroanalysis 1995 Volume 7, Issue 4 Pages 333-339
A. P. Doherty, M. A. Stanley, G. Arana, C. E. Koning, R. H. G. Brinkhuis, J. G. Vos

Abstract: The synthesis, characterization and applications of the redox polymer [Os (bipy)2 (PS)7.5 (DMAP)2.5 Cl]Cl where bipy = 2,2'-bipyridyl, PS = polystyrene and DMAP = poly[4-(N-methyl-N-p-vinylbenzylamino)pyridine] are described. The polymer was characterized by spectrophotometry, luminescence, cyclic voltammetry and chronoamperometry. Modified electrodes were prepared by droplet evaporation of a 1% solution of the polymer on to 3 mm vitreous C electrodes. Electrochemical measurements were performed using SCE reference and Pt counter electrodes. The modified electrodes were applicable to the determination of Fe; the polymer mediated the reduction of Fe(III). The kinetic behavior was similar at rotating disc electrodes and in thin-layer flow cells. Fe was determined in pharmaceuticals by FIA using the modified electrodes as detectors. The carrier electrolyte was 0.1 M H2SO4 (1 ml/min) and the applied potential was -0.05 V vs. SCE. The calibration graph was linear for 10^-1000 µM-Fe(III) and the detection limit was 3 µM. The results agreed well with those obtained by spectrophotometry. The polymer was stable for 7 days.
Iron Electrode Electrode Electrode Method comparison

"Determination Of Codeine In Human Plasma And Drug Formulation Using A Chemically Modified Electrode"
Electroanalysis 1998 Volume 10, Issue 8 Pages 536-540
Jyh-Myng Zen*, Ming-Ren Chang, Hsieh-Hsun Chung, Ying Shih

Abstract: Both flow injection methodology and square-wave voltammetry were developed and evaluated for determining codeine in human blood plasma and pharmaceutical formulations using a Nafion/Ru oxide pyrochlore chemical modified electrode. Combining the electrocatalytic function of the Ru oxide pyrochlore with charge-exclusion and the pre-concentration features of Nafion perform well in codeine detection. Compared to a bare glassy C electrode, the chemical modified electrode exhibits a shift of the oxidation potential in cathodic direction and a marked enhancement of the current response. A linear calibration plot is obtained over the 0-32 µM range in 0.05 M HClO4 solution with a detection limit (3s) of 10 nM in the square-wave voltammetric method. While, in flow injection anal., a linear calibration plot is obtained over the 0.5-40 µM range with a detection limit of 0.86 ng. Quant. anal. was performed by the standard addition method for codeine content in human plasma and a commercial available drug.
Codeine Electrode Electrode Voltammetry Method comparison Apparatus Detector

"Horseradish Peroxidase Immobilized Electrode For Phenothiazine Analysis"
Electroanalysis 1998 Volume 10, Issue 18 Pages 1241-1248
Christine Petit, Kazuo Murakami, Arzum Erdem, Emrah Kilinc, Gemma Ortiz Borondo, Jean-Fran&ccedil;ois Liegeois, Jean-Michel Kauffmann

Abstract: A horseradish peroxidase (HRP) immobilized carbon composite electrode has been developed for the amperometric study of phenothiazine analogs. Flow injection analysis and batch experiments have been realized in acetate buffer in the presence of hydrogen peroxide. Cyclic voltammetry and amperometry using a thin-layer flow cell (dual configuration, serial mode) have permitted one to suggest the mechanisms governing the biosensor signal at -0.1 V (vs. Ag/Ag+), in the presence of hydrogen peroxide, by addition of a phenothiazine derivative It was inferred that electron transfer mediation by the phenothiazine occurred at HRP/graphite adsorbed sites, in addition to peroxidn. by dispersed HRP with substrate recycling at the graphite array-like structure of the biosensor. Thanks to these processes, high sensitivities were achieved especially in batch configurations, with amperometric detection capabilities down to 10^-8 M in acetate buffer pH 4.7. Application of the biosensor to the determination of phenothiazines in drug formulations were realized.
Drugs Phenothiazine Electrode Electrode Amperometry Sensor Apparatus Detector

"Determination Of Trace Levels Of Oxytocin In Pharmaceutical Solutions By High Performance Liquid Chromatography"
J. Chromatogr. A 1987 Volume 410, Issue 1 Pages 157-168
David S. Brown and Dennis R. Jenke

Abstract: An automated system is described that consists of an Alltech C18 Universal guard cartridge (used as pre-concentration. column) and a column (12.5 cm x 4.6 mm) packed with Partisphere C18. The mobile phase was acetonitrile - 0.1% H3PO4 (21:79) with fluorescence detection at 418 nm (excitation at 250 nm). Post-column derivatization was carried out with fluorescamine(I) reagent, and a reaction buffer which was added separately from the I solution via a dual-pump reactor system. The pre-concentration. and analysis of adjacent samples were timed to occur concurrently. The coefficient of variation (n = 64) was <1.5% with a recovery of ~100% and a detection limit of ~15 ng.
Oxytocin HPLC Fluorescence Post-column derivatization

"Liquid Chromatography-mass Spectrometry With Ionspray And Electrospray Interfaces In Pharmaceutical And Biomedical Research"
J. Chromatogr. A 1991 Volume 554, Issue 1-2 Pages 39-46
A. P. Bruins

Abstract: Electrospray and ionspray techniques use samples that exist as ions or ion-molecule complexes in solution. After the dispersion of the solution into an electrically charged aerosol, the sample ions may escape from the solution into the gas phase in a region that is at atmospheric pressure. The sample ions are transported into the mass analyzer. which is operated under a high vacuum. Liquid chromatographs can be coupled to electrospray and ionspray interfaces. Flow injection or continuous infusion of a sample solution (both without the use of a separating column) may be preferred over online liquid chromatography-mass spectometry in certain applications. Electrospray or ionspray is applicable to polar or ionic samples. Weakly polar and apolar samples are not ionized under electrospray or ionspray conditions. Applications of the techniques are in the fields of drug metabolism, natural product analysis and the determination of high molecular weights through the observation of multiply charged ions.
Ionic strength LC Mass spectrometry Dispersion

"Liquid Chromatography-mass Spectrometry In The Pharmaceutical Industry: Objectives And Needs"
J. Chromatogr. A 1982 Volume 251, Issue 2 Pages 141-151
F. Erni

Abstract: The role of liquid chromatography-mass spectrometry (LC-MS) in the analysis of drugs is discussed. The main fields of application are thermally labile compounds, compounds with low volatility and compounds with rather high molecular weights, all of which are not generally suitable for analysis by combined gas chromatography-mass spectrometry. The objectives, needs, limitations and abilities of LC-MS for the analysis of by-products, degradation products, traces of drug substances for pharmacokinetic studies and metabolites in complex matrices are presented. The LC-MS coupling is discussed as a sophisticated LC detector for sensitive and selective quantitative determinations or as an online sample-introduction system for the mass spectrometer to obtain structural information for identification or structural elucidation. LC-MS combined with a flow-switching technique can be used for the analysis of mixtures containing large amounts of components which otherwise would be detrimental to the LC-MS technique. With flow injection techniques the LC-MS interface is used as a sample-introduction system with possibilities for sample preparation, sample clean-up and chemical derivatization.
Drugs HPLC Mass spectrometry Interface Review

"Analysis Of Aluminum In Pharmaceutical Products By Post-column Derivatization Ion Chromatography"
J. Chromatogr. A 1994 Volume 671, Issue 1-2 Pages 115-120
J. Carnevale and P. E. Jackson*

Abstract: Pharmaceutical sample (5 ml), such as injectable glucose, saline solution or water, was boiled with 100 µL of 5 M H2SO4 for 5 min, and the solution was cooled and diluted to 10 mL with water. A 50 µL portion was injected on to a column (7.5 cm x 7.5 mm i.d.) of Waters Protein-Pak SP-5PW cation exchanger, with 0.1 M K2SO4 of pH 3 as the mobile phase at a flow-rate of 1 ml/min. The eluate was treated with a solution of 4 mM 8-hydroxyquinoline-5-sulfonic acid and 2 mM cetyltrimethylammonium bromide in 1 M acetate buffer of pH 4.4 in a knitted PTFE reaction coil. Fluorescence detection was carried out at excitation 395 nm and emission 500 nm. The response to Al was linear in the range 2-1200 ng/ml, the detection limit was 0.5 ng/ml for a 50 µL injection and the RSD were 2-3% and 1% for 50 and 100 ng/ml Al standards, respectively. The average recovery for 10^-1200 ng/ml of Al was 99% with a RSD of 5%. There was no interference from the matrix or transition metals and the results agreed with those obtained by ICP-AES.
Aluminum HPIC Spectrophotometry Interferences 8-hydroxyquinoline-5-sulfonic acid Knotted reactor Post-column derivatization

"Low-pressure Ion Chromatography"
J. Chromatogr. A 1994 Volume 671, Issue 1-2 Pages 23-28
Xinshen Zhang* and Xiaoping Jiang

Abstract: Two types of instrument, a low-pressure fast analysis ion chromatograph and a low-pressure transition metal ion chromatograph, were used with conductivity and optical detectors, respectively, in the analysis of a variety of ions. Both systems were operated at 30-40 psi using 30 mm long columns packed with spherical particles of ion exchanger. The conditions are described for the determination of alkali metals and NH4+, alkaline earth metals, inorganic anions and organic acids using conductivity detection and transition metals using post-column derivatization with a chromogenic reagent and optical detection. An improved conductivity cell is described which has an electrode at the solution entry end for high sensitivity. The detection limit for each ion was generally 10-9 g/ml. The technique was applied to the analysis of acid rain and Chinese medicines and the determination of Na+, K+ and chloride in blood and Fe2+, Zn2+ and Mn2+ in oilfield water.
Metals, alkali Metals, alkaline earth Metals, transition Ammonium Anions, inorganic Acids, organic HPIC Chromogenic reagent

"Use Of Liquid Chromatography-nuclear Magnetic Resonance Spectroscopy For The Identification Of Impurities In Drug Substances"
J. Chromatogr. A 1994 Volume 677, Issue 2 Pages 385-389
John K. Roberts* and Richard J. Smith

Abstract: Impurities at the 3% level were detected in drug substances by HPLC-NMR. Analysis was performed on a Spherisorb S5 ODS2 column (25 cm x 4.6 mm i.d.) with acetonitrile/0.05 M potassium dihydrogen orthophosphate (2:3) of pH 3.5 in 2H2O as mobile phase (1 ml/min), injection volumes of 100 and 200 µL and UV detection. The outlet of the UV detector was connected to the NMR spectrometer (40 MHz). 1H spectra were recorded in the flow and stopped-flow modes. Synthetic mixtures of drug related compounds were used to show that good quality 1H data was obtained from sample quantities of 25-50 µg injected on-column in reasonable accumulation times (30 min). The system was used to identify an impurity in a real sample. The 1H spectrum of the impurity indicated the presence of two methyl groups, olefinic protons and the presence of a 1,2 disubstituted aromatic ring. The impurity was identified from the NMR data and confirmed by UV spectrophotometry.
HPLC Nuclear magnetic resonance Spectrophotometry Stopped-flow

"Enantiomeric Resolution Of Primary Amines By Capillary Electrophoresis And High Performance Liquid Chromatography Using Chiral Crown Ethers"
J. Chromatogr. A 1994 Volume 680, Issue 1 Pages 253-261
Yvonne Walbroehl* and Joseph Wagner

Abstract: Two complementary methods are described for the analysis of primary amines of pharmaceutical interest. Capillary electrophoresis separations were performed using a fused-silica capillary (57 cm x 75 µm i.d.; effective length 50 cm), mainly using 50 mM sodium phosphate buffer of pH 2.2 containing 30 mM 18-crown-6 tetracarboxylic acid and detection at 254 or 280 nm, depending on the analyte. For poor UV absorbing analytes, 6 mM benzyltrimethylammonium chloride of pH 3.7 was substituted for sodium phosphate, with indirect detection at 214 nm. HPLC separations were performed on a 5 µm CrownPak(+) column (15 cm x 4 mm i.d.) with a 30-50 µm glass bead guard column (2.1 cm x 2.0 mm i.d.). Various mobile phases were used, mostly based on HClO4 (0.0011-0.16M) and 15% methanol at pH 0.98-2.92 and temperatures of 30 or 40°C with various detector wavelengths and post-column derivatization with o-phthalaldehyde and fluorescence detection in some cases. Analogues of aminotetralin, aminodecalin, aminomethylbenzodioxane, aminonaphthalene and aminophenanthrene were examined. Results are tabulated.
Amines, primary HPLC Electrophoresis Crown ether

"Development Of A Simple Liquid Chromatographic Method With UV And Mass Spectrometric Detection For The Separation Of Substances Related To Amoxicillin Sodium"
J. Chromatogr. A 1998 Volume 797, Issue 1-2 Pages 311-316
L. Valvoa, E. Cirannia,*, R. Alimentia, S. Alimontia, R. Draiscib, L. Giannettib and L. Lucentinib

Abstract: The development of a selective method for the separation and identification of amoxicillin sodium-related substances is described. It is based on reversed-phase liquid chromatography followed either by UV detection (LC-UV) or by mass spectrometry (LC-MS). Mass detection was carried out by an atmospheric pressure ionization source and ion-spray interface. Flow injection analysis-MS gavepositive-ion mass spectra exhibiting abundant peaks due to their protonated molecules without significant fragmentation. The protonated molecules were used for selected ion monitoring LC-MS analyzes. The method allowed the resoln. of 13 available potential impurities from amoxicillin and from each other. Its applicability to an MS detector also permits a rapid identification of the impurities in the lack of the corresponding reference substances.
Amoxycillin Mass spectrometry Mass spectrometry

"Flow Injection Analysis. A New Approach To Pharmaceutical Determinations"
J. Pharm. Biomed. Anal. 1985 Volume 3, Issue 2 Pages 105-121
Angel R&iacute;os, M. Dolores Luque De Castro and Miguel Valc&aacute;rcel*

Abstract: A review is presented of flow injection analysis, particularly automated multiple flow injection analysis, closed-loop systems and the use of electroanalytical techniques in conjunction with flow injection analysis for pharmaceutical applications. (113 references).
Closed loop Review

"FIA - Extraction Applied To The Limit Test For Heavy Metals"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 8 Pages 937-945
Lars-G&ouml;ran Danielsson* and Zhao Huazhang

Abstract: Heavy metals in various samples were determined by flow injection extraction - spectrophotometry (e.g., at 274 nm) as their diethyldithiocarbamate complexes. Analytical parameters were chosen such that the sensitivities for toxic metals were enhanced compared with those for less toxic ones; e.g., at pH 3.5 in the presence of 3 mM EDTA the response to Fe, Mn, Ni and Zn was suppressed, but that to Pb was not. Calibration was effected with standard Pb solution, and the heavy metal content was calculated as Pb. The system was more sensitive than the standard procedure based on precipitation of colloidal sulfides. Relative responses for various ions at pH 3.5 and 4.7 in the presence and absence of EDTA are reported, as are results obtained on analytical-grade salts, pharmaceutical raw materials and household commodities. A method is presented that allows rapid determination of the total concentration of heavy metals in a sample. The method is based on FIA-extraction and photometric measurement of the metals as their dithiocarbamate complexes. The analytical parameters have been chosen such that the sensitivities for toxic elements are enhanced compared with those of less toxic heavy metals. The sampling capacity of the system is 40 samples h-1 and the repeatability (RSD) is 1.9% at 0.1 mg 1-1. Raw materials for the production of pharmaceuticals as well as analytical grade salts and household commodities have been tested.
Metals, heavy Lead Spectrophotometry Sample preparation Sensitivity Calibration Extraction Complexation

"Oxidative Column For The Flow Injection Analysis - Spectrophotometric Determination Of Paracetamol"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 10 Pages 1165-1172
J. Martinez Calatayud* and S. Sagrado Vives

Abstract: In a flow injection system, paracetamol was oxidized4 at room temperature in ammoniacal solution with K3Fe(CN)6 immobilized on an anion-exchange column. The N-acetyl-p-benzoquinonimine produced was allowed to react at 80°C with phenol, giving a blue product the absorbance of which was measured at 630 nm. The calibration graph was rectilinear from 0.20 to 20 ppm and the coefficient of variation was 0.6% (n = 40). Throughput was 42 samples per h. Paracetamol was determined in several pharmaceutical formulations.
Acetaminophen Spectrophotometry Oxidation column Heated reaction Resin

"Rapid-scan Hydrodynamic Voltammetry And Cyclic Voltammetry Of Pharmaceuticals In Flow Injection Analysis Conditions"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 12 Pages 1479-1483
L. J. Nagels*, G. Mush and D. L. Massart

Abstract: An online rapid-scan electrochemical detector is described for use in HPLC and flow injection analysis comprising a flow cell (diagram given), a potentiostat, a computer and interfacing equipment. The detector can be operated under convection/diffusion-controlled and diffusion-controlled conditions. An online rapid-scan electrochemical detector is described for use in HPLC and flow injection analysis comprising a flow cell (diagram given), a potentiostat, a computer and interfacing equipment. The detector can be operated under convection/diffusion-controlled and diffusion-controlled conditions. An on-line rapid-scan electrochemical detector is described for HPLC and FIA systems. Its practical use in qualitative analysis is demonstrated for 19 drug substances. The detector can be operated to record convection/diffusion-controlled (S-shaped), or diffusion- controlled (peak-shaped) voltammograms. In the latter mode, on-line cyclic voltammetry measurements are possible. The cell can also be used as an amperometric detector for conventional, microbore and micro-LC methods. Detection limits are of the order of 10 pg (conventional and microbore HPLC), or at the sub-picogram level (micro-LC). For scanning work, drugs can be analyzed at mg L-1 levels in an FIA setup.
Drugs HPLC Voltammetry Voltammetry Detector Computer Diffusion

"Flow Injection Analysis Of Pharmaceuticals"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 12 Pages 1291-1300
M. D. Luque de Castro* and M. Valc&aacute;rcel

Abstract: An overview of the most representative problems solved by flow injection analysis (FIA) in drug analysis is presented. Different aspects of this technique which can be manipulated with specific purposes are discussed and special emphasis is placed on the possibilities of FIA in dissolution test control. 102 references.
Drugs Review Dissolution rate

"Solid-state PVC Flow-through Benzoate Electrode"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 12 Pages 1499-1505
Jos&eacute; L. F. C. Limaa,*, M. Concei&ccedil;&atilde;o, B. S. Montenegroa, J. Alonsob, J. Bartrolib and J. G. Raurichb

Abstract: Flow injection manifolds are described which incorporate a tubular electrode of a construction based on that previously described by Alegret et al. (Anal. Chim. Acta, 1984, 164, 147) with PVC membrane electrodes comprising tetraoctylammonium benzoate and 2-nitrophenyl octyl ether. Response was rectilinear down to 0.1 and 0.3 mM benzoate (I) with single-channel and double-channel flow injection manifolds, respectively. Corresponding detection limits were 70 µM and 0.1 mM I. The double-channel system was applied in the determination of I in pharmaceuticals.
Benzoate Electrode Electrode Electrode Electrode

"FIA Determination Of Chlorhexidine By Means Of The Precipitation With Copper(II)"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 12 Pages 1441-1445
J. Martinez Calatayud*, a and J. V. Garcia Mateob

Abstract: Sample solution (89 µL) was injected into a stream of 0.35 M NH3 - 1 mM Cu solution (0.7 mL min-1). The ppt. formed was collected, washed for 4 min with 0.35 M NH3 (3.5 mL min-1) and dissolved in a stream of 1 M HNO3 (4 mL min-1). The resulting Cu2+ was determined by AAS at 324.8 nm. The calibration graph was rectilinear from 5 to 20 ppm. The coefficient of variation was 3.6% and the sample throughput was 10 h-1. The determination of chlorhexidine in pharmaceutical formulations is carried out using flow injection analysis (FIA) with measurement by atomic absorption spectrometry (AAS). The method is based on the formation of a copper-biguanide complex precipitate when the sample is injected into an ammoniacal copper solution. The precipitate is retained on a plastic or paper filtering device. A nitric acid stream dissolves the precipitate and carried the Cu(II) to the AAS detector. The chlorhexidine is determined over the range 5-20 ppm. The influence of interfering substances is investigated.
Chlorhexidine Spectrophotometry Complexation Interferences Precipitation Indirect Filter

"Determination Of Aminoglycosides In Pharmaceutical Formulations. 2. High Performance Liquid Chromatography"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 12 Pages 1711-1718
H. Fabre*, M. Sekkat, M. D. Blanchin and B. Mandrou

Abstract: Samples were prepared as described by Sekkat et al. (cf. Ibid,. 1989, 7, 883), but with final dilution to 75 µg mL-1 for gentamicin and 25 µg mL-1 for other aminoglycosides. HPLC was carried out on a stainless-steel column (25 cm x 4 mm) of LiChrosorb RP18 (7 µm) in series with a guard column (4 mm x 4 mm) of the same material and with 0.2 M Na2SO4, 0.02 M Na pentanesulfonate and 1% acetic acid in aqueous 3% methanol or (for Kanamycin A and B) 0.05 M Na2SO4, 25 mM Na pentanesulfonate and 0.1% acetic acid in aqueous 0.5% acetonitrile as mobile phase (2 mL min-1). Post-column derivatization was carried out with phthalaldehyde reagent (prep. described) in a reaction coil (4.5 m x 0.25 mm) at 0.58 mL min-1. Fluorimetric detection was at 440 nm (excitation at 340 nm). Rectilinear calibration ranges, detection limits and coefficient of variation, obtained for various aminoglycosides, are tabulated.
Aminoglycosides HPLC Fluorescence Post-column derivatization

"Rapid Determination Of Benzalkonium Chloride In Pharmaceutical Preparations With Flow Injection Liquid-liquid Extraction"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 3 Pages 243-252
J. J. Halvax*, G. Wiese, J. A. Arp, J. M. P. Vermeer, W. P. Van Bennekom and A. Bult

Abstract: Benzalkonium chloride was assayed by online extraction of the benzalkonium ion with picrate to chloroform. The absorbance of picrate was measured. The extractions were performed with a home-made flow injection extraction unit. Calibration curves (1.5-180 x 10^-4% w/v) were straight lines (r = 0.9993) and the relative standard deviation of a series of injections was less than or equal to 2%. Pharmaceutical benzalkonium preparations, containing xylometazoline, timolol, phenylephrine or carbachol could also be assayed. The method was compared with a modified HPLC assay. A flow injection extraction unit is described; the determination is based on the ion-pair extraction of benzalkonium chloride (I) with picrate. Sample solution was mixed with 0.4 mM picrate buffer in the mixing coil of the apparatus followed by extraction of the resulting ion-pair into CHCl3 and measurement of absorbance at 370 nm. The calibration graph was rectilinear from 1.5 to 1800 ppm of I and was prepared from peak-height measurements. The influence of flow rates, the extraction behavior of the I - picrate complex and the adsorption of I on the tubing walls of the apparatus are discussed. The possible interference from other drugs is discussed. Pharmaceutical I preparations containing xylometazoline, timolol, phenylephrine or carbachol were also analyzed.
Benzalkonium chloride Drugs Spectrophotometry Sample preparation Calibration Solvent extraction Interferences Method comparison

"Automation Of Pharmaceutical Dissolution Testing By Flow Injection Analysis"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 4 Pages 329-336
M. D. Luque de Castro and M. Valc&aacute;rcel

Abstract: The different types of instruments used for monitoring pharmaceutical dissolution testing are presented. Their features and the need for automation are critically discussed. The advantages of flow injection analysis in this respect are illustrated by a variety of examples clearly showing its adaptability to the different problems posed by other automatic and non-automatic alternatives. Existing instruments for monitoring dissolution testing of pharmaceuticals are discussed with particular reference to the need for automation. The application of flow injection analysis to interface between dissolution vessels and analytical instruments is described.
Automation Dissolution rate Interface Review

"Spectrophotometric Determination Of Adrenaline With An Oxidative Column In A FIA Assembly"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 8-12 Pages 663-666
A. Kojo and J. Martinez Calatayud*

Abstract: A single channel FIA assembly is proposed for the spectrophotometric determination of adrenaline, the aqueous sample solution is directly injected into the carrier stream leading the sample through a manganese dioxide column at 80°C, and on to the spectrophotometer flow-cell. The calibration graph is linear up to 17 ppm of adrenaline. The influence of other substances has been studied and the method has been applied to the determination of adrenaline in a pharmaceutical formulation. Sample solution (348.8 µL) was injected into a carrier stream (0.55 mL min-1) of distilled and de-areated water and passed through a column of MnO2, the carrier solution, sample loop and column were maintained at 80°C. The absorbance of the oxidized sample was measured at 300 nm. The calibration graph was rectilinear up to 17 ppm of adrenaline and the detection limit was 0.05 ppm. Coefficient of variation was 0.19% (n=11). Sample throughput was 45 h-1. Interference was present from procaine, amethocaine and picric acid.
Adrenaline Spectrophotometry Column Flowcell Calibration Interferences Oxidation column Heated reaction

"FIA - Fluorimetric Determination Of Thiamine"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 8-12 Pages 667-670
J. Martinez Calatayuda,*, C. Gomez Benitob and D. Gaspar Gimeneza

Abstract: Sample solution (137.3 µL) was injected into a carrier stream (0.74 mL min-1) of Na2CO3 - boric acid (pH 10) into a coil column (225 cm length) containing immobilized hexacyanoferrate on an ion-exchange resin (cf., Calatayud and Sagrado Vives, Ibid., 1989, 7, 1165) and the fluoresence of the eluate was measured at 440 nm (excitation at 368 nm). Calibration graphs were rectilinear from 0.1 to 4.0 ppm of thiamine. Coefficient of variation was 1.8%. Sample throughput was 28 h-1. Other vitamins, e.g. riboflavin, nicotinamide, pyridoxin, and certain other substances, e.g. caffeine, gave errors of up to 4.3%. A flow injection fluorimetric determination of thiamine is reported. The procedure is based on the oxidation of the analyte with potassium hexacyanoferrate(III) immobilized on an anionic exchange resin; the fluorescence is monitored in aqueous basic solution. Concentrations of the vitamin of 0.1-4 ppm have been determined; the relative standard deviation was 1.8%. The injection rate was 28 samples/h. The influence of other substances and the determination of the drug in a pharmaceutical formulation are also reported.
Thiamine Fluorescence Ion exchange pH Column Immobilized reagent Resin Calibration Interferences Oxidation column

"Indirect Continuous Automatic Determination Of Pharmaceuticals By Atomic Absorption Spectroscopy"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 8-12 Pages 655-661
M. Valc&aacute;rcel*, M. Gallego and R. Montero

Abstract: The implementation of continuous separation techniques such as precipitation, liquid-liquid and solid-liquid extraction in FIA manifolds coupled online with an atomic absorption spectrometer for the determination of active components (sulfonamides, local anaesthetics, amphetamines, benzodiazepines, chloramphenicol and methadone) in pharmaceuticals and biological fluids is systematically described. The basic features of the analytical methodologies described (sensitivity, selectivity, precision and rapidity) are also discussed and critically compared. The use is described of continuous separation techniques such as, precipitation, liquid - liquid and solid - liquid extraction in flow injection analysis manifolds coupled online to an AA spectrometer for the determination of active components in pharmaceuticals and biological fluids. Sulfonamides were pptd. with Cu standard solution (more selective) or Ag ions at pH 6 to 7, filtered and the filtrate was measured by AAS. Anaesthetics were pptd. with Co ions. Recoveries were quantitative. The continuous liquid-liquid extraction technique was based on the method described by Nord and Karlberg (Anal. Chim. Acta, 1981, 125, 199) and was applied in the determination of amphetamines and bromazepam. Solid-phase redox columns were used for those compounds with potentially reducible groups, e.g. sulfone, N-oxide groups. The basic features (sensitivity, selectivity, precision and rapidity) of the analytical methods described are discussed.
Bromazepam Amphetamines Anaesthetics Spectrophotometry Sample preparation Automation Precipitation Extraction pH Selectivity Sensitivity Filtration Reduction column Indirect

"Vitamins B1 And B6 Tubular Electrodes As FIA Detectors; Their Use In The Analysis Of Pharmaceutical Products"
J. Pharm. Biomed. Anal. 1991 Volume 9, Issue 10-12 Pages 1041-1046
Jos&eacute; L. F. C. Lima*, M. Concei&ccedil;&atilde;o B. S. M. Montenegro and A. M. R. Silva

Abstract: Ion-selective electrodes without an inner reference solution and tubular potentiometric detectors for the determination of vitamins B1 and B6 in pharmaceutical preparations by flow injection analysis (FIA) are reported. The membranes were prepared with the vitamin tetra(2-chlorophenyl)borate (TCPB) dissolved in o-nitrophenyloctyl ether (o-NPOE) and immobilized on PVC. Intrinsic behavior of the tubular detectors was assessed using a low-dispersion single-channel FIA manifold and was compared with conventionally-shaped electrodes using the same membrane. Data obtained in the determination of vitamins B1 and B6 in pharmaceutical preparations with a double channel flow injection manifold incorporating the tubular detectors are presented and compared with those obtained by the U.S. Pharmacopeia method and by direct potentiometry with conventionally-shaped electrodes. Ion-selective electrodes without an inner reference solution and tubular potentiometric detectors were constructed using membranes prepared with tetra(2-chlrorophenyl)borate dissolved in o-nitrophenyloctyl ether and immobilized on PVC. The tubular detectors were used with a double channel flow injection manifold to determine vitamins B1 and B6 in pharmaceuticals.
Vitamin B1 Vitamin B6 Pyridoxine Thiamine Electrode Electrode Potentiometry Membrane Method comparison Standard method

"Determination Of Mitoxantrone By Flow Injection Analysis Using An Amperometric Detector"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 4 Pages 263-267
Juan Carlos Cortina Villar, Agust&iacute;n Costa Garc&iacute;a and Paulino Tu&ntilde;&oacute;n Blanco*

Abstract: Sample solution was injected into a carrier stream (4 mL min-1) of 0.1 M perchloric acid of pH 1.12 and mitoxantrone (mitozantrone; I) was determined by oxidation at a carbon paste electrode at +0.9 V vs. Ag - AgCl. The calibration graph was rectilinear for 0.05 to 10 µM I; the detection limit was 0.11 µM. The method was used to determine I in pharmaceuticals. Mitoxantrone was determined by flow injection analysis using a flow cell modified in the lab. and fitted with carbon paste as an amperometric detector. The sample solution (100 µL, 5 x 10^-8-1 x 10^-5M) was injected into the carrier stream of 0.1 M HClO4 (pH 1.12). Mitoxantrone was determined by oxidation at the carbon paste electrode at +0.90 V. A 60-cm delay coil (0.5 mm i.d.) was incorporated just before the detector (a canal thin-layer) and a flow rate of about 4 mL min-1 was used. The system was successfully applied to the mitoxantrone determination in a pharmaceutical preparation; the method was fast and reproducible.
Mitozantrone Amperometry Electrode

"Determination Of The Preservative, Chlorocresol, In A Pharmaceutical Formulation By Flow Injection Analysis"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 775-778
M. S. Bloomfield* and K. A. Prebble

Abstract: A flow injection analysis procedure is described for the determination of chlorocresol (I) in a parenteral pharmaceutical preparation, based on the Liebermann spot test for phenol. Neat sample (20 µL) was injected into a carrier stream (0.5 mL min-1) of water which was merged with a reagent stream (1.8 mL min-1) of nitrous acid and passed through a PTFE reaction coil (2 m x 0.5 mm) before spectrophotometric detection at 400 nm. The calibration graph was rectilinear from 0.05 to 0.15% of I. Recoveries were 97.6 to 99.9% and the coefficient of variation was 0.6%. The method should be applicable to other pharmaceutical products and to other compounds containing a phenolic ring. A flow injection analysis (FIA) procedure is described for the determination of chlorocresol (4-chloro-3-methylphenol) in a parenteral pharmaceutical formulation. The product was directly injected into a carried stream of water and subsequently reacted with a reagent stream of nitrous acid. The resulting brown nitro-derivative was determined spectrophotometrically at 400 nm. The method was validated and should be applicable to chlorocresol in other pharmaceutical products and to compounds containing a phenolic ring, assuming absence of matrix interference.
Chlorocresol Spectrophotometry Interferences

"Determination Of Pentavalent Antimony In Sodium Stibogluconate In A Pharmaceutical Formulation By Flow Injection Analysis"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 779-783
M. S. Bloomfield*, A. D. Dow and K. A. Prebble

Abstract: Injection solution (2 ml) was ultrasonicated with 2 M H2SO4 (20 ml) for 5 min, 20% aqueous tartaric acid (100 ml) was added and the mixture was diluted to 200 mL with water. A 20 µL portion of the solution was injected into an aqueous 1% KI carrier stream (0.5 mL min-1) which was merged with a 2 M H2SO4 stream (1.8 mL min-1) and passed through a reaction coil (4 m x 0.5 mm) before spectrophotometric detection at 350 nm. Closed conditions prevented interference from atmospheric O; interference from side reactions was minimized due to the rapid reaction time. The calibration graph was rectilinear from 0.05 to 0.15% of Sb(V). Recoveries were 98.7 to 103.7%; the coefficient of variation (n = 8) was 0.9%. Assuming absence of matrix interference, the method should be applicable to the determination Sb5+ from other sources and to other reducible ionic species. A flow injection analysis (FIA) procedure is described for the determination of pentavalent antimony (Sb(V)) in the drug, sodium stibogluconate, in a parenteral pharmaceutical formulation (Pentostam). The sample solution is injected directly into a carrier stream of iodide ion which is then mixed with an acid stream in situ. Sb(V) is determined by the redox reaction with acidified iodide to release iodine, which is monitored spectrophotometrically at 350 nm. The closed conditions prevent interference from atmospheric oxygen and the rapid reaction time assists in minimizing interference from side reactions. The use of tartaric acid as a solvent for sample and standard solutions ensures obedience of Beer's law over the Sb(V) and Sb(III), and has been fully validated for use in a pharmaceutical preparation Assuming absence of matrix interference it is applicable to Sb(V) from other source and should be applicable to other reducible ionic species.
Antimony(5+) Spectrophotometry Indirect Interferences

"Novel Flow Injection Analysis Systems For Drug Analysis"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 769-773
Gary D. Christian

Abstract: Principles of operation and advantages of a cam-driven sinusoidal-flow syringe pump are described for use in conventional FIA or sequential injection analysis (SIA). SIA is a modified flow method that allows most analyzes to be performed on a single line with only one syringe. The apparatus is relatively cheap, readily automated and easily adaptable to different chemical methods. Flow injection coulometric titration is described as a valuable technique for analysis of unstable reagents or standards. Acid-base, redox, precipitation and complexometric titrants can be generated electrochemically, as can unstable titrants such as Cu(I), Br, Cl and Cr(II). The techniques described have potential for automatic drug assays. A review with 32 references. Flow injection analysis (FIA) has become a versatile tool for rapid and automated analysis. As its capabilities have increased, so have the complexity and operation of the apparatus. Ways to simplify both the apparatus and the application of injection techniques are investigated. A novel cam-driven syringe pump and the development of sequential injection analysis (SIA) are discussed, and some applications presented. Flow injection coulometric titrations. are presented as a means to further alleviate reagent stability and calibration problems. These systems have potential for automatically carrying out many drug assays.
Drugs Coulometry Titrations Sequential injection Pump Apparatus Review

"Spectrophotometric Determination Of Promazine With An Oxidative Column In FIA Manifolds"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 785-788
Anatol Kojlo*, Helena Puzanowska-Tarasiewicz and J. Martinez Calatayud

Abstract: Two flow injection methods for the determination of promazine hydrochloride (I), using MnO2 oxidative columns and spectrophotometric detection of the oxidation product at 513 nm were developed. Method (i) involved direct sample injection (250 µL) into a HCl carrier stream by a loop-valve injector; in this instance the oxidative column (11 cm x 1 mm) was placed between the sample injector and the detector. Method (ii) involved the introduction of the sample into the sample loop which also acted as the oxidative column (optimum length 24 cm). In both methods a HCl carrier stream of pH 1.6 was used at a flow rate of 0.8 mL min-1. Calibration graphs were rectilinear from 2 to 20 mg L-1 and from 1 to 6 mg L-1 of I for methods (i) and (ii), respectively; corresponding detection limits were 0.1 and 0.03 mg l-1. Sampling rates were 62 and 80 h-1 for methods (i) and (ii), respectively. Results obtained compared well with those of the method of Blasek and Kracmar (cf. Ceskoslov Farm., 1967, 16, 437). A simple flow injection spectrophotometric method for the determination of promazine is described. The two proposed procedures are based on the oxidation of analyte with a manganese dioxide column. Concentrations of promazine in the ranges 2-20 and 1-6 are determined with a relative standard deviation of 1.0%. The injection rates are 62 and 80 samples h-1, respectively. The influence of foreign species and the determination of promazine in a pharmaceutical formulation are also reported.
Promazine Spectrophotometry Oxidation column Column Optimization Interferences

"Determination Of Thiol-containing Drugs By Chemiluminescence-flow Injection Analysis"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 1 Pages 15-20
P. Vi&ntilde;as*, I. Lopez Garcia and J. A. Martinez Gil

Abstract: Sample was dissolved in water and a portion of resulting solution was introduced into an FIA system (diagram given), consisting of 5 mM luminol in 0.1 M KOH - boric acid buffer (pH 10.4), 50 µM Cu(II) and 10 mM H2O2 at 7.2 mL min-1; chemiluminescent detection was used. Calibration graphs were rectilinear from 0.1 to 10 mM of cysteine, penicillamine and 2-thiouracil and 0.2 to 10 mM of N-acetylcysteine and 2-mercaptopropionylglycine. The coefficient of variation were from 1.2% and 2.1%. A flow injection analysis procedure with chemiluminescence detection for the determination of both thiol-containing drugs and the amino acid cysteine is described. Procedures are based on the inhibition by the drugs of the chemiluminescence generated in the copper-catalyzed oxidation of luminol by hydrogen peroxide. The proposed methods were applied to the determination of cysteine, N-acetylcysteine, penicillamine, 2-mercaptopropionylglycine and thiouracil in pharmaceuticals.
Drugs Cysteine Penicillamine Thiouracil N-acetylcysteine 2-Mercaptopropionylglycine Chemiluminescence Catalysis

"Determination Of Captopril In Pharmaceutical Samples By Flow Injection Analysis"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 10 Pages 887-891
M. I. Albero, C. S&aacute;nchez-Petre&ntilde;o*, M. S. Garci&aacute; and V. R&oacute;denas

Abstract: A flow injection spectrophotometric method for the determination of captopril involving measurement of the absorbance of the captopril complex with palladium(II) in a 0.12 M HCl medium at 400 nm is presented. The calibration graph was linear over the range 2 x 10^-5-6 x 10^-4 M. The sampling frequency was 90 h-1 with sample injections of 70 µL. The proposed method was applied to the determination of captopril in pharmaceutical samples. Powdered tablets were shaken with water for 10 min and the solution was filtered. A 70 µL portion of the filtrate was injected into a carrier stream of water (3.3 ml/min) which was then merged with a stream of 5 mM PdCl2 in 0.12 M HCl (3.3 ml/min) before passing through a reaction coil (90 cm x 0.5 mm i.d.) and measurement of absorbance at 400 nm. The sample injection volume, dimensions of the reaction coil and the flow rate were optimized. The calibration graph was linear from 20-600 µM-I, the detection limit was 2.2 µM and the RSD (n = 10) was 0.6% at 4 mM I. Recoveries (tabulated) were >98.9% and the sampling frequency was 90/h. No interference was observed from excipients and additives to the dosage forms.
Captopril Spectrophotometry Interferences

"Online Photoreaction And Fluorimetric Determination Of Diazepam"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 11-12 Pages 1357-1360
R. Segarra Guerrero, C. Gomez Benito and J. Martinez Calatayud*

Abstract: Sample solution containing ~20 µg/ml of diazepam was prepared in 0.04 M NaOH containing 6 µg/ml of Cu2+ and the solution was irradiated for 5 min in the PTFE loop (3 m x 0.5 mm i.d.) of a single-channel FIA assembly (illustrated). A Vilber-Lurmat T-60 Hg lamp was used for the irradiation. The sample was then injected into a carrier stream (3 ml/min) of water and transferred to a Perkin-Elmer LS-50 fluorimetric detector with a Hellma flow cell (inner volume 20 µL). The fluorescence was measured at 362 nm (excitation at 319 nm). The calibration graph was linear for 0.5-50 µg/ml of diazepam, with an RSD (n = 10) of 2.1% at 7 µg/ml. The method is less sensitive than chromatographic methods, but provides a simple and rapid procedure for pharmaceutical samples, with a sample throughput of 10/h.
Diazepam Fluorescence Photochemistry Method comparison

"Copper Carbonate As A Solid-bed Reactor For Spectrophotometric Determination Of Doxycycline And Oxytetracycline In An Unsegmented Continuous-flow Assembly"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 11-12 Pages 1093-1098
J. L. Lopez Paza and J. Martinez Calatayudb,*

Abstract: The flow injection analysis-spectrophotometric determination of doxycycline was carried out by reaction of the drug with cupric ions entrapped in a polymeric material in a packed-bed reactor: the complex formed was then injected into a manifold with an alkaline solution as carrier. The developed color was monitored at 395.0 nm. The method was applied to the determination of doxycycline in different pharmaceutical formulations. The calibration graph for doxycycline hyclate was linear over the range 10.0-80.0 mg mL-1 (n = 8) with a relative standard deviation of 1.4% (at 25 mg mL-1) and a sample throughput of 128 h-1. The proposed procedure was also applied to the determination of oxytetracycline in pharmaceutical formulations. The reactor was prepared (cf. Lahuerta Zamora et al., Anal. Chim. Acta, 1992, 265, 81; Garcia Mateo and Martinez Calatayud, Ibid., 1993, 274, 275) by stirring 16.6 g of CuCO3.Cu(OH)2.2H2O and 17.4 g of Reposa AL-100-A polyester resin solution followed by the addition of ethyl methyl ketone as polymerization catalyst. The solid obtained was dried at room temperature for 2-3 h and reduced to small particles. Portions of the sieved particles (150-200 µm) were washed with water at 80°C, sieved again, and placed in a PTFE tube (8.5 cm x 1.5 mm i.d.). Sample solution of doxycycline (I) from capsules or injections were prepared in 0.1 M or 0.5 M HCl and diluted as appropriate, and adjusted to pH2.0-2.2. Portions were injected into a flow manifold consisting of the bed reactor column and a carrier flow line carrying 0.029 M NaOH to meet the sample flow line after the column. The flow rates were 3.72 ml/min, and detection was at 395 nm. The calibration graph was linear for 18-80 mg/ml of I and the RSD was 1.4% at 25 mg/ml. The same procedure could be used for the determination of oxytetracycline. The flow injection analysis-spectrophotometric determination of doxycycline was carried out by reaction of the drug with cupric ions entrapped in a polymeric material in a packed-bed reactor: the complex formed was then injected into a manifold with an alkaline solution as carrier. The developed color was monitored at 395.0 nm. The method was applied to the determination of doxycycline in different pharmaceutical formulations. The calibration graph for doxycycline hyclate was linear over the range 10.0-80.0 mg mL-1 (n = 8) with a relative standard deviation of 1.4% (at 25 mg mL-1) and a sample throughput of 128 h-1. The proposed procedure was also applied to the determination of oxytetracycline in pharmaceutical formulations.
Doxycycline Spectrophotometry

"Automated Flow Injection Technique For Use In Dissolution Studies Of Sustained-release Formulations: Application To Iron(II) Formulations"
J. Pharm. Biomed. Anal. 1994 Volume 12, Issue 5 Pages 635-641
Constantinos A. Georgioua, Georgia N. Valsamib, Panayotis E. Macherasb and Michael A. Koupparisa,*

Abstract: Formulations were dissolved in 0.1 M HCl (procedure described), screened and 100 µL aliquots injected into the 0.1 M HCl carrier (0.66 ml/min) and mixed with 0.1% ferrozine, [3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine monosodium salt] containing ascorbic acid (anti-oxidant) in 0.5 M acetate buffer of pH 3.7, (2.62 ml/min) and the mixture passed through a reaction coil (100 cm). The Fe(II) complex (ε = 28 000) was mixed with further acetate buffer (3.96 ml/min) in a second coil (100 cm) and absorbance measured at 562 nm. A computer program was used to optimise the system and chemical parameters with respect to throughput and sensitivity. The calibration graph was linear for 1-130 ppm of Fe(II). Two calibration graphs were constructed: absorbance at maximum peak height (1-70 ppm); and from absorbance at the descending part of the FIA peak (2-130 ppm). RSD was 3% (n = 3). Recoveries from commercial formulations ranged from 99.2 to 103.2%. The application of flow injection analysis (FIA) to automated dissolution studies of sustained-release formulations is described. The long-term stability of the dissolution-FIA analyzer. was checked during unattended operation for 42 h. The construction of multiple calibration curves with the so-called electronic dilution FIA procedure was used to extend the linear range of the determination. The computer-controlled FIA system and the principles of associated software are described and applied to dissolution studies of sustained-release formulations of iron(II) using its sensitive reaction with the color reagent, ferrozine. The extended linear range of the determination is 1-130 ppm iron(II) and the precision (RSD) better than 3% (n = 3).
Iron(2+) Spectrophotometry Dilution Linear dynamic range Dissolution rate Optimization Buffer Computer

"Flow Injection Determination Of Novalgin Using Amperometric Detection At A Glassy Carbon Electrode"
J. Pharm. Biomed. Anal. 1994 Volume 12, Issue 9 Pages 1109-1113
Tom&aacute;s P&eacute;rez-Ruiz*, Carmen Mart&iacute;nez Lozano and Virginia Tom&aacute;s

Abstract: An electroanalytical study of the oxidation of Novalgin (dipyrone) at a glassy carbon electrode in aqueous solution has been carried out. A flow injection method with amperometric detection based on this oxidation process is also described. The influence of flow rate, coil length and injection volume on the sensitivity of the method was established. The calibration graph was linear within the range 3 x 10^-6 - 3 x 10^-5 M in an ammonia buffer solution (pH 9) as a potential of 0.4 V versus an Ag/AgCl reference electrode. The sampling rate was 54 samples h-1. The applicability of the method to the determination of Novalgin in pharmaceutical preparations was demonstrated by investigating the effect of potential sources of interference and by analyzing commercial preparations.
Drugs Novalgin Electrochemical analysis Electrode Electrode Amperometry Sensor Interferences

"Kinetic Determination Of Nortriptylin In Pharmaceutical Samples By Use Of Photometric And Fluorimetric Detection"
J. Pharm. Biomed. Anal. 1995 Volume 13, Issue 3 Pages 199-203
L. de la Pe&ntilde;a, A. G&oacute;mez-Hens and D. P&eacute;rez-Bendito

Abstract: A fast kinetic method is proposed for the photometric and fluorimetric determination of nortriptyline hydrochloride. The method involves measuring the rate of formation of an adduct with 4-chloro-7-nitrobenzofurazan, which exhibits light absorption and fluorescent properties, and the use of a stopped-flow mixing technique, which facilitates application to automatic routine analyzes. The reaction rate is measured within only 30 s. The detection limit is 0.12 g mL-1 (photometry) and 0.18 g mL-1 (fluorimetry) and the calibration graph is linear up to 60 g mL-1 in both cases. The precision (as RSD) is less than 1.5%. The proposed method was satisfactorily used for direct analysis of pharmaceutical preparations and a mean recovery near 100% was obtained with both photometric and fluorimetric detection.
Drugs Nortriptyline Fluorescence Spectrophotometry Kinetic

"Flow Injection Extraction-spectrophotometric Determination Of Bromhexine With Orange IV"
J. Pharm. Biomed. Anal. 1995 Volume 13, Issue 9 Pages 1101-1106
Tomas P&eacute;rez-Ruiz*, Carmen Mart&iacute;nez-Lozano, Antonio Sanz and Santos Mondejar

Abstract: Sample (60 µL) containing bromhexine (I) was injected into a stream (0.9 ml/min) of 0.5 M chloroacetate buffer of pH 3 which merged with a stream (0.9 ml/min) of aqueous 0.3 mM orange IV solution [4-(p-anilinophenyl-azo)benzene sulfonic acid sodium salt]. After passing through a reaction coil (30 cm x 0.5 mm i.d.) the resulting stream merged with a stream (1.3 ml/min) of 1,2-dichloroethane and passed through an extractor coil (100 cm x 0.5 mm i.d.), then through a phase separator incorporating a PTFE membrane permeable only to the organic phase. The absorbance of the organic phase was measured at 421 nm. The calibration graph was linear for 5-160 µM-I and the detection limit was 0.5 µM. The RSD were 0.32-0.88% (n = 10). Sample throughout was 40/h. Tolerance limits of foreign compounds are tabulated. The method was applied to TCA-treated human serum with recoveries of 98.5% and to a pharmaceutical preparation with recoveries of 100.5-102%. An automatic flow injection photometric method for the determination of bromhexine is proposed. The drug was determined by formation of an ion- pair with orange IV, extraction into 1,2-dichloroethane and measurement of the absorbance at 412 nm of the organic phase. A linear calibration graph was obtained at concentrations of 5 x 10^-6-1.6 x 10^-4 M of bromhexine. Up to 40 samples h-1 can be processed with an RSD of 0.32- 0.88%. The method was applied to the determination of bromhexine in blood serum and a pharmaceutical preparation.
Bromhexine Spectrophotometry Sample preparation Extraction Organic phase detection Phase separator Teflon membrane

"Flow Injection Spectrophotometric Determination Of Promazine"
J. Pharm. Biomed. Anal. 1996 Volume 14, Issue 3 Pages 267-271
Helena Puzanowska-Tarasiewicz, Elbieta Woyniec* and Anatol Kojo

Abstract: Promazine hydrochloride was dissolved in water and injected into a carrier stream (1.6 ml/min) of water. The carrier stream then merged with a reagent stream (1.6 ml/min) of 10 mM molybdophosphoric acid and passed through a reaction coil (2 m x 0.8 mm i.d.). The absorbance was measured at 524 nm. The calibration graph was linear for 1-25 ppm promazine hydrochloride with a detection limit of 0.35 ppm. The RSD (n = 20) for 10 ppm promazine hydrochloride was 1.8%. The effects of interferences on the methods are discussed.
Promazine hydrochloride Spectrophotometry Interferences

"Colorimetric Determination Of Astemizole In Bulk And In Its Pharmaceutical Dosage Forms Using Flow Injection"
J. Pharm. Biomed. Anal. 1996 Volume 14, Issue 5 Pages 579-582
A. A. Alwarthan* and A. M. Al-Obaid

Abstract: A flow injection spectrophotometric method