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 -> tablet

Citations 197

"Flow Injection Analysis Of Amlodipine Using UV-detection"
Pharmazie 2002 Volume 57, Issue 7 Pages 500-500
Altiokka, G.; Altiokka, M.

Abstract: A method for the direct determination of amlodipine in tablets by flow injection analysis without colorizing the solutions was presented.
Amlodipine Spectrophotometry

"Sensitive Assay For Clavulanic Acid And Sulbactam In Pharmaceuticals And Blood Serum Using A Flow Injection Chemiluminometric Method"
Anal. Chim. Acta 2000 Volume 414, Issue 1-2 Pages 15-23
Fatma A. Aly, Nawal A. Alarfaj and Abdulrahman A. Alwarthan

Abstract: A sensitive, simple and inexpensive chemiluminescence (CL) method using flow injection is described for the determination of two β-lactamase inhibitors sulbactam sodium and clavulanic acid (potassium salt) in their pure form, in pharmaceutical preparations and added to blood serum. The method is based on the enhancing effect of these compounds on the CL generated by the oxidation of luminol with hydrogen peroxide in alkaline medium. The CL intensity is a linear function of sulbactam sodium concentration over the range 0.1-150 µg mL-1 with a detection limit (2 x noise) of 0.05 µg mL-1, and for clavulanic acid over the range 0.01-12 µg mL-1 with a detection limit of 0.01 µg mL-1. The method is applied successfully to the determination of the drugs in their dosage forms without interference from co-formulated drugs. The method is specific for the intact drugs in the presence of their degradation products.
Clavulanic acid Sulbactam Chemiluminescence Indirect Optimization Method comparison

"A New Simple And Accurate Turbidimetric Method For Determination Of Ascorbic Acid In Pharmaceuticals And Fruits"
J. Chin. Chem. Soc. 2002 Volume 49, Issue 5 Pages 949-956
Mir Ali Farajzadeh and Sepideh Nagizadeh

Abstract: An accurate, simple, solvent free and inexpensive turbidimetric method is presented for the determination of ascorbic acid in pharmaceutical preparations and fruits. It needs no special reagents or precautions. In this method HgCl2 oxidizes ascorbic acid in citrate buffer at a pH of about 4 and produced Hg2Cl2 precipitate as monitored by turbidance measurements. The procedure is very simple and the experimental conditions such as temperature, ionic strength, stirring and time are not critical. High sensitivity and selectivity are two other advantages of this method. Linear dynamic range of the calibration curve is between 3-120 µg/mL with limit of detection (LOD) 1 µg/mL, which allows the ascorbic acid contents of most fruits and vegetables to be analyzed. On the other hand, the interference studies show that common compounds in real samples and colored substances have no considerable effect on the determination. Only filtration of some samples is necessary and other treatments, which are performed prior to determination of ascorbic acid by other analytical methods, are eliminated. Finally, ascorbic acid concentration in different samples is determined by the proposed method and obtained results are compared with the results of the official 2,6-dichlorophenolindophenol or iodimetric methods and a good agreement is obtained. This method is very sensitive in comparison with iodimetry and is very fast relative to the 2,6-dichlorophenolindophenol method.
Ascorbic acid Turbidimetry Interferences Optimization Method comparison

"Simultaneous On-line Dissolution Monitoring Of Multicomponent Solid Preparations Containing Vitamins B1, B2"
Anal. Chim. Acta 2000 Volume 408, Issue 1-2 Pages 39-47
Wei Li, Jian Chen, Bingren Xiang and Dengkui An

Abstract: A unique stopped-flow flow injection analysis system for simultaneous synchronous spectrofluorimetric on-line dissolution monitoring of multi-component solid preparations that makes use of a fiber-optic sensor was presented. A new means of in vitro therapeutic drug monitoring was developed by hyphenating the fiber-optic sensor technique and a chemometric method. An artificial neural network method was applied to construct the mathematical model for the simultaneous analysis of the mixture of vitamins B-1, B-2 and B-6 by synchronous spectrofluorimetry. The selection of the wavelength interval, the pH of the carrier solution and other experimental conditions were investigated, and discussed. The proposed method has been applied to the dissolution monitoring of vitamin B tablets with satisfactory results. The recovery was 97.8-105%, and the relative standard deviation was 1.1-7.5%, The dissolution parameters of vitamins B-1, B-2 and B-6 in the vitamin B complex tablets, which were derived from a best mathematical model using the proposed method, were furnished. The system could provide a profitable new technique for simultaneous on-line process monitoring of therapeutic drugs and their metabolites in biological body fluids.
Vitamin B1 Vitamin B2 Vitamin B6 Fluorescence Sensor Stopped-flow Chemometrics Neural network Dissolution rate

"Chemiluminescence Behavior Of The Decomposition Of Hydrogen Peroxide Catalyzed By Copper(II)-amino Acid Complexes And Its Application To The Determination Of Tryptophan And Phenylalanine"
Anal. Chim. Acta 2000 Volume 409, Issue 1-2 Pages 65-73
Soichi Hanaoka, Jin-Ming Lin and Masaaki Yamada

Abstract: A weakly chemiluminescent (CL) emission has been observed during the decomposition of hydrogen peroxide catalyzed by copper(II) in basic aqueous solution. On adding an appropriate amount of amino acid solution into the mixed solution of hydrogen peroxide and copper(II), a strong CL emission was recorded. This CL emission depends on the kind of amino acid. The CL emissions for tryptophan and phenylalanine were fast, but for other amino acids, they were relatively slow. In the presence of a low concentration of carbonate in the basic solution, the CL emission was enhanced for ail amino acids. This CL system was developed for the determination of amino acids with a flow injection system. The detection limits of tryptophan and phenylalanine were 4.5 x 10^-6 and 1.1 x 10^-5 MI respectively. After the liquid chromatographic separation of tryptophan and phenylalanine by means of an ODS-80Ts column (5 µm, 250 mm x 4.6 mm i.d.) with water as eluent, the present CL system was used as a post-column detector for these two amino acids in tablets without any special labeling treatment.
Tryptophan d-Phenylalanine Chemiluminescence Kinetic Indirect Post-column derivatization

"Spectrofluorimetric Kinetic Determination Of Selenium (IV) By Flow Injection Analysis In Cationic Micellar Medium"
Talanta 2000 Volume 51, Issue 2 Pages 225-230
Afsaneh Safavi and Mohammad Mirzaee

Abstract: A sensitive catalytic kinetic spectrofluorimetric method for determining ng mL-1 of selenium by flow injection analysis has been developed. The method, based on the catalytic effect of Se (IV) on the reduction of resorufin by sulfide, in the presence of cetylpyridinium chloride, is monitored spectrofluorimetrically (lambda(ex) = 480 nm; lambda(em) = 583 nm). The linearity range of the calibration graph is dependent on the concentration of sulfide. The variables affecting the rate of the reaction were investigated.:The method is simple, rapid, precise, sensitive, and widely applicable. The limit of detection is 1 ng mL-1 Se (IV), and the calibration range is 5-1000 ng mL-1. Sampling rate is 60 samples hr-1, and the relative standard deviation of 12 determinations of 100 ng mL-1 Se was 0.76%. The determination of Se (IV) in the presence of Se (VI) and total selenium is described. The method was applied to the determination of Se in selenium tablets, and several synthetic samples.
Selenium(IV) Selenium, total Fluorescence Catalysis Micelle Surfactant Kinetic Indirect Speciation Interferences Optimization Triton X

"On-line Assay Of S-captopril Using An Amperometric Biosensor/sequential Injection System"
Anal. Chim. Acta 2000 Volume 411, Issue 1-2 Pages 51-56
Raluca-Ioana Stefan, Jacobus (Koos) F. van Staden and Hassan Y. Aboul-Enein

Abstract: An automated system for the enantiopurity test of S-captopril based on the concept of sequential injection analysis (SIA) with an amperometric biosensor (based on L-amino acid oxidase (L-AAOD)) as detector is described. The proposed system is fully computerised and is suitable for the on-line monitoring of S-captopril at a sampling rate of 80 samples per hour with an RSD <0.22% in the linear range between 0.05 and 1.50 µmol/l. The detection limit is 16 nmol/l.
Captopril Amperometry Sensor Sequential injection Computer Interferences Method comparison

"Determination Of Ofloxacin Using A Chemiluminescence Flow Injection Method"
Anal. Chim. Acta 2000 Volume 416, Issue 2 Pages 227-230
Yi Rao, Yan Tong, Xinrong Zhang, Guoan Luo and Willy R. G. Baeyens

Abstract: A new chemiluminescence (CL) flow injection method was proposed for the determination of ofloxacin in pharmaceuticals in the range 0.04-4 µg mL-1 with a detection limit of 0.016 µg mL-1 and a relative standard derivation (RSD) of 2.2% at 0.4 µg mL-1 (n=10). The method is based on the CL reaction of cerium(IV) with sulfite sensitized by ofloxacin. The established procedure could be applied to the determination of ofloxacin in tablet, capsule and injection in agreement with the results obtained by using reported methods.
Ofloxacin Chemiluminescence Method comparison

"Extraction Based On The Flow Injection Principle. 2. Determination Of Codeine As The Picrate Ion-pair In Acetylsalicylic Acid Tablets"
Anal. Chim. Acta 1979 Volume 104, Issue 1 Pages 21-28
Bo Karlberg, Per-Arne Johansson and Sidsel Thelander

Abstract: Codeine phosphate (I phosphate) [52-28-8] in aqueous samples was extd. as its picrate ion pair into CHCl3 in a continuous-flow system. The sample was introduced into an aqueous picrate stream buffered at pH 6.5; its dispersion gave controlled mixing before the aqueous stream was segmented by a CHCl3 stream. A specially constructed fitting is included to produce segments, typically 5-10 mm long, which passes into a Teflon coil (2 m long: inner diameter, 0.8 mm). At the outlet of the coil, the phases were separated and a fraction of the CHCl3 phase was passed through a spectrophotometric flow cell. The sample volume was 25-40 µ, the sampling rate ~60/h, and the relative standard deviation 1%.
Codeine Spectrophotometry Sample preparation Ion pair extraction Buffer Organic phase detection

"Preconcentration And Differential Pulse Voltammetry Of Butylated Hydroxyanisole At A Carbon Paste Electrode"
Anal. Chim. Acta 1983 Volume 154, Issue 1 Pages 87-94
Joseph Wang and Bassama A. Freiha

Abstract: Butylated hydroxyanisole (I) and tocopherols were pre-concentrated by accumulation on carbon-paste electrodes (2.5 g of Acheson graphite, grade 38, plus 1.5 g of Dow Corning silicone grease). After pre-concentration for 5 min, a detection limit of ~20 µM-I was obtained. Enhanced selectivity was achieved by transferring the electrode to an electrolytic blank solution before the measurement step; this enabled the surface-bound species to be measured without interference from species in solution The differential pulse stripping response was evaluated with respect to concentration. dependence, reproducibility, pre-concentration period, detection limit and other variables. The cited method was used in the selective detection of I in a flow injection system based on a recently developed manifold procedure (Anal. Chem., 1983, 55, 1285). The method was applied to, e.g., soft drinks, maize oil and multivitamin tablets.
Butylated hydroxyanisole Tocopherols Electrode Voltammetry Interferences Preconcentration

"Pharmaceutical Applications Of A High Performance Flow Injection System"
Anal. Chim. Acta 1986 Volume 181, Issue 1 Pages 241-244
F. P. Bigley and R. L. Grob, G. S. Brenner

Abstract: The system, which utilizes the design concepts of HPLC combined with post-column reaction and spectrophotometric detection, allows minimum set-up and changeover time between samples, and produces accurate and precise results at sample rates of up to 1200 h-1. A 10-port loop injector with a 15 µL sample loop and a reaction/equilibration tube (2 ft x 0.005 in.) were used with direct measurement of the absorbance of the analyte in solution in water or 0.1 M HCl and a flow rate of 2 mL min-1. Hydrochlorothiazide(I) was determined at this sample rate with a coefficient of variation (n = 10) of 0.64% and timolol maleate at 720 samples h-1 with a coefficient of variations of 1.16%. Methyldopa, amiloride and I were determined together in tablets at a rate of 450 h-1. Methyldopa was also determined by spectrophotometric measurement of its instantly formed reaction product with Fe(II) tartrate with use of a reaction tube (2 ft x 0.01 in.) and a flow rate of 2 mL min-1.
Drugs Amiloride Hydrochlorothiazide Methyl dopa Spectrophotometry Post-column derivatization

"Chemiluminescence Determination Of Buprenorphine Hydrochloride By Flow Injection Analysis"
Anal. Chim. Acta 1986 Volume 185, Issue 1 Pages 329-333
Abdul A. Alwarthan and Alan Townshend

Abstract: The sample solution (52 µL) was injected into a stream of 50 mM polyphosphoric acid (2.3 mL min-1) and passed through a tube (24 cm x 0.9 mm), before mixing with a stream of 10 µM-KMnO4 (2.3 mL min-1). The mixed streams were passed through a reaction coil of glass tubing (34 cm x 2.3 mm) and chemiluminescence was measured. Log. - log. calibration graphs were rectilinear from 10 nM (detection limit) to 0.1 mM buprenorphine hydrochloride(I). In the determination of 10 µg mL-1 of I, the coefficient of variation was 0.7% (n = 10). The method was applied to tablets containing 0.2 mg of I.
Drugs Buprenorphine hydrochloride Chemiluminescence

"Fluorimetric Determination Of Danthron In Pharmaceutical Tablets And In Urine"
Anal. Chim. Acta 1987 Volume 192, Issue 2 Pages 293-299
Blair E. Miller and Neil D. Danielson

Abstract: A flow injection system used for determination of danthron(I) in pharmaceutical samples was composed of a loop injector (30 µL) and a 150-cm mixing coil containing 90 mM Na2S2O4 in methanol - aqueous 2% Na2B4O7 (1:1) as carrier (1.2 mL min-1). A spectrofluorimeter fitted with a 3.5 µL flow cell was used to monitor emission at 510 nm (excitation at 388 nm). Rectilinear calibrations were achieved from <0.1 to 30 µg mL-1 of I with a detection limit of 0.01 µg mL-1. Urine samples required pre-separation by HPLC in a 5 µm C1 silica column (25 cm x 4.5 mm) with aqueous 70% methanol as mobile phase (1.2 mL min-1). The eluate was mixed with the carrier of the flow injection system (0.4 mL min-1). A rectilinear calibration graph was obtained for 0.02 to 2 µg mL-1 of I, with a detection limit of 6 ng mL-1.
Danthron HPLC Fluorescence

"Automated Flow Injection Determination Of Sulfonamides By The Bratton-Marshall Reaction For Clinical Analysis, Assays And Dissolution Studies Of Formulation"
Anal. Chim. Acta 1988 Volume 204, Issue 1-2 Pages 271-283
M. A. Koupparis and P. I. Anagnostopoulou

Abstract: Two flow injection manifolds are described based on the Bratton - Marshall reaction, one for 2 to 20 mg L-1 of sulfonamide and the other for 0.5 to 5 mM. N-(1-Naphthyl)ethylenediammonium chloride is used as chromogenic reagent with detection at 545 nm. The method was used in the determination of sulfonamides in serum, urine, feeds and formulations, and for automated dissolution studies of tablets. The detection limit was 0.6 to 1.1 mg l-1, and the coefficient of variation was <0.5% (n = 10). The analysis rate was 72 samples h-1. The pseudo-titrimetric method gave a 1.3% mean difference from the HPLC technique.
Sulfonamides Clinical analysis Spectrophotometry Dissolution rate Method comparison Chromogenic reagent

"Chemiluminescence Detection Of The Benzodiazepine Loprazolam"
Anal. Chim. Acta 1989 Volume 227, Issue 1 Pages 65-71
Anthony R. J. Andrews and Alan Townshend

Abstract: Of seven such compounds tested only loprazolam gave any significant emission after oxidation, e.g., by KMnO4. The optimum conditions used in a 0.5 mm i.d. PTFE tubing dual-flow injection system were: 0.2 mM KMnO4, with 0.94 M formic acid (at pH 0.9) as the carrier stream at 1.3 mL min-1 in both lines. The response was rectilinear between 10 µM and 5 mM for a 50 µL injection, and the limit of detection was 7 µM. Iron(II) and Mn(II) interfered. The method was applied in analysis of tablets, but results were rather higher than expected.
Loprazolam Benzodiazepine, derivatives Chemiluminescence Optimization pH Interferences Redox

"Flow Injection Spectrofluorimetric Determination Of Paracetamol"
Anal. Chim. Acta 1990 Volume 231, Issue 1 Pages 259-264
J. Martinez Calatayud, C. Gomez Benito

Abstract: Duolite A102 D anion-exchange resin (Probus) was saturated with K3Fe(CN)6 solution and slowly stirred for 30 min. The resin was separated and washed with water until a colorless filtrate was obtained. Oxidative mini-columns, prepared by introducing the resin into PTFE coils, were incorporated into the flow injection assembly (diagram given). Powdered tablets containing paracetamol (I; 0.04 to 17.6 mg l-1) were dissolved in water and the solution was applied to the mini-columns followed by direct injection into a stream of Na2CO3 - H3BO3 - KCl buffer (pH 9.94) which then merged with a stream of N,N'-dimethylformamide in an inert single-bead string reactor. Fluoresence detection was at 427 nm (excitation at 331 nm). The calibration graph was rectilinear from 0.04 to 100 mg L-1 of I and the coefficient of variation was 1.4%. Tolerance levels for foreign species are tabulated and the determination of I in several pharmaceutical formulations is discussed.
Acetaminophen Ion exchange Fluorescence Resin Interferences Buffer pH Calibration Oxidation column Single bead string reactor

"Continuous-flow Determination Of Reserpine By Oxidation With Periodate Ion And Catalysis By Manganese(II) In Solution Or By An MnO2 Reactor"
Anal. Chim. Acta 1990 Volume 233, Issue 2 Pages 235-241
S. R. Varma, J. Martinez Calatayud and Horacio A. Mottola

Abstract: Reserpine oxidation by periodate, catalyzed by Mn(II) or Mn(IV), in acidic medium, produced yellow 3,4-didehydroreserpine which could be detected spectrophotometrically at 385 nm. The solid MnO2 was thermally embedded on the walls of Tygon tubing and incorporated in the flow system in an open-tubular reactor. Both methods were easily adapted for rapid, repetitive continuous-flow determinations. The detection limit with the Mn(II) system was 5.0 or 7.5 µM, the coefficient of variation (n = 10) was ~2% and the throughput was 60 samples h-1. The figures for the MnO2 reactor were not as good, but this method was simpler and showed remarkable stability and reproducibility. Fluorimetric detection could be used if a lower detection limit was required. The methods were used to analyze single reserpine tablets and Rauwolfia serpentina standard powders.
Reserpine Spectrophotometry Catalysis Detection limit Solid phase reagent

"Indirect Flow Injection Determination Of Methadone By Atomic Absorption Spectrometry"
Anal. Chim. Acta 1990 Volume 234, Issue 2 Pages 433-437
R. Montero, M. Gallego and M. Valc&aacute;rcel

Abstract: Methadone (I) is determined in tablets and urine in the presence of other drugs after reduction on a Cd or Zn micro-column and flame AAS detection of the metal ions released. For urine, a 5 mL sample is made alkaline with NaOH and extracted with CH2Cl2. The residue from evaporation of the extract, is dissolved in water, and the solution is adjusted to pH 4.0 with 0.01 M acetic acid. Crushed tablet (200 mg) is dissolved in water by shaking for 55 min and filtering. The final solution (90 µL), at pH 3.3 to 4.3, is injected into a carrier stream of water (3.0 mL min-1) which proceeds to the reduction column (8.5 cm x 1.8 mm) and subsequently to the spectrometer. The calibration graph is rectilinear from 5 to 50 ng mL-1 of I. Recoveries from either column are quantitative, and coefficient of variation in urine (n = 3) are 1.2 to 3.0%. Sampling frequency is 150 h-1, and other drugs do not interfere.
Methadone Spectrophotometry Sample preparation Column pH Calibration Interferences Extraction Indirect Reduction column

"Flow Injection Spectrophotometric Determination Of Ascorbic Acid By Reduction Of Vanadotungstophosphoric Acid"
Anal. Chim. Acta 1991 Volume 243, Issue 2 Pages 187-190
D. Thorburn Burns N. Chimpalee, D. Chimpalee and S. Rattanariderom

Abstract: Ascorbic acid may be determined spectrophotometrically at 360 nm based on reduction of vanadotungstophosphoric acid using flow injection analysis. The carrier stream was distilled water and the reagent streams were buffer solution (pH 3.0), 1.735 times 10^-3 M dodecatungstophosphoric acid and 1.735 times 10^-3 M sodium vanadate. The injection rate was 80 h-1. The calibration graph was linear up to 80 µg mL-1 ascorbic acid and the relative standard deviation for the determination of 20 µg mL-1 ascorbic acid was 1.5% (n = 10). The detection limit was 1.0 µg mL-1 ascorbic acid, based on an injection volume of 250 µl. The system was applied to the determination of ascorbic acid in vitamin C tablets. Sample solution (250 µL) was injected into a carrier stream of water which was mixed with acetate buffer solution (pH 3.0), and this mixture was merged with pre-mixed 1.735 mM dodecatungstophosphoric acid solution and 1.735 mM sodium vanadate solution (each at 1.55 mL min-1). The mixture was passed through a reaction coil (3 m x 0.8 mm) and the reduction of vanadotungstophosphoric acid was monitored at 360 nm. The calibration graph was rectilinear up to 80 µg mL-1 of ascorbic acid, with a detection limit of 1 µg mL-1. The coefficient of variation was 1.5% (n = 10) for 30 µg mL-1. Semicarbazide interfered positively and SO32- interfered negatively. The sampling rate was 80 h-1. The method was applied to vitamin C tablets.
Ascorbic acid Spectrophotometry

"Photochemical Derivatization And Spectrofluorimetric Determination Of Chlorpromazine By Flow Injection"
Anal. Chim. Acta 1992 Volume 256, Issue 1 Pages 105-111
J. Mart&iacute;nez Calatayud*, C. G&oacute;mez Benito

Abstract: Chlorpromazine hydrochloride (I) in 0.146 mM HCl solution was passed through a 300-cm PTFE tube helically coiled around a UV lamp in a continuous-flow manifold. The max. photo-oxidation was achieved using 254-nm radiation at a flow rate of 3.32 mL min-1, with a sample volume of 682 µL. The solution was passed to a fluorimetric detector for recording of the emission spectra (excitation 358 nm, emission 298 nm). The calibration graph was rectilinear in the range 31 ng to 6.24 µg mL-1 of I. In the determination of 0.56 µg mL-1 of I, the coefficient of variation of peak height was 1.9% (n = 34) and the injection rate was 59 samples h-1. The method was used for the determination of I in tablets and suppositories. The influence of excipients is discussed.
Chlorpromazine Fluorescence Photochemistry Interferences UV reactor

"Flow Injection Spectrophotometric Determination Of Acetaminophen In Drug Formulations"
Anal. Chim. Acta 1992 Volume 261, Issue 1-2 Pages 261-267
Krishna K. Verma, Archana Jain and Kent K. Stewart*

Abstract: The sample solution in 0.1 M HCl (50 µL) is injected into a carrier stream of 0.1 M HCl, and the resulting solution is merged with an oxidizing reagent comprising aqueous 0.2% Na 2-iodylbenzoate. The stream passes through a knitted reaction coil (25 cm x 0.5 mm) before detection of the quinonimine reaction product at 445 nm in an 8 µL flow-through cell. The rectilinear calibration range is 0.8 to 100 mg L-1 of paracetamol and the detection limit is 0.8 mg l-1. Sample throughput is 360 h-1. Slight interference is caused by dipyrone, ascorbic acid, isoniazid and SO32-, but excipients and numerous other drugs do not interfere. The method has been applied to 0.1 M HCl extracts of paracetamol tablets. Results agreed well with those obtained by LC. A flow injection method is described for the determination of acetaminophen (paracetamol) (linear range 0.8-100 µg mL-1) based on its oxidation with 2-iodylbenzoate in acid medium to produce a yellow-orange compound, believed to be N-acetyl-1,4- benzoquinoneimine, which is monitored at 445 nm. The sample throughput is 360 h-1. The precision (RSD) of determination was 0.5-2%. The method was applied to the determination of acetaminophen in drug formulations, and evaluated by analyzing spiked sample solutions, a mean recovery of 100.6% (range 96.3-105.2%) being obtained. No interference was observed from the common excipients of drugs and other active substances, e.g., dipyrone, acetylsalicylic acid, salicylamide and oxyphenbutazone. The possible application of the proposed method in content uniformity test and drug dissolution studies is indicated. Comparison of the present method with a liquid chromatography method for acetaminophen determination gave a mean difference of 1.2% (range 0.4-2.4%).
Acetaminophen Spectrophotometry Method comparison Interferences Knotted reactor

"Entrapment Of Reagents In Polymeric Materials: Indirect Atomic Absorption Spectrometric Determination Of Isoniazid By Oxidation With Manganese Dioxide Incorporated In Polyester Resin Beads In A Flow Injection System"
Anal. Chim. Acta 1992 Volume 265, Issue 1 Pages 81-86
L. Lahuerta Zamora, J. V. Garcia Mateo and J. Martinez Calatayud*

Abstract: A method for entrapment of reagents is described. The experimental procedure is based on the dispersion of the reagent (MnO-2) into an unsaturated polyester solution and grinding the product to give the required particle size (300-400 µm). The reagent is packed into a bed reactor (1.5 mm i.d.) and incorporated into a flow injection system. The procedure was used for the indirect atomic absorption spectrometric determination of isoniazid (0.5-10 µg mL-1) solutions of pharmaceutical products, with little interference from excipients. The measurements are based on the determination of Mn-2+ released onoxidation of the isoniazid. The relative standard deviation for the determination of 5 µg mL-1 of isoniazid is 2.57% (n = 40) and the sample throughput is 43 h-1. The oxidizing agent MnO2 was homogenized with a polyester resin solution (Al-100) and mixed with ethyl methyl ketone. The solid was dried for 2 to 3 h at room temperature and ground to give the required particle size (300 to 400 µm). The reagent was packed into a PTFE tube (1.5 mm i.d.) to form a bed reactor and placed in a flow injection manifold for the indirect determination of isoniazid (I) by AAS of the released Mn2+ at 279.5 nm. A solution containing 20 µg mL-1 of the drug was injected into a carrier stream of 5 mM H2SO4 at a flow-rate of 4.5 mL min-1 and at room temperature The optimum sample volume was 811 µL and column length was 21.4 cm. The calibration graph was rectilinear in the range 0.50 to 10 µg mL-1 of I, the coefficient of variation was 2.6% at the 5.0 µg mL-1 level (n = 40) and the throughput rate was 43 samples h-1. The method was applied to the determination of I in tablets.
Isoniazid Spectrophotometry Indirect Solid phase reagent Resin Oxidation column Interferences

"Spectrophotometric Determination Of Cardiac Glycosides By Flow Injection Analysis"
Anal. Chim. Acta 1992 Volume 269, Issue 2 Pages 199-203
P. Solich*, V. Sedliakov&aacute; and R. Karl&iacute;ek

Abstract: An optimized flow injection analysis method was described for the determination of lanatoside A, B and C, digoxin, digitoxin, acetyldigitoxin and ouabain, based on their reaction with picric acid in alkaline media and spectrophotometric detection at 486 nm. The flow injection manifold (diagram given) consisted of a FIA 20 Analyser linked to a Zeiss Spekol 10 photometer; the flow rate was 0.6 mL min-1 through the PTFE reaction coil (200 cm) with a sample volume of 100 µL. The calibration graph was rectilinear for 0.025 to 0.5 g L-1 for the cited glycosides (except ouabain) and from 0.01 to 0.2 g L-1 for ouabain; coefficient of variation (n = 6) were 0.6 to 2.2%. Sample throughput was 60 h-1. An optimized flow injection method for the determination of various cardiac glycosides (lanatoside A, B and C, digoxin, digitoxin, acetyldigitoxin, and ouabain) was based on their reaction with picric acid in alkaline media with spectrophotometric detection at 486 nm. The calibration graph was linear for 0.025-0.5 g L-1 cardiac glycosides (except ouabain) and 0.01-0.2 g L-1 ouabain, with relative standard deviation between 0.62 and 2.16% and a sample throughput of 60 h-1. This method was utilized for the determination of digoxin in tablets and lanatoside C, and ouabain in injections.
Glycosides Lanatoside A Lanatoside B Lanatoside C Digitoxin Acetyldigitoxin Digoxin Ouabain Spectrophotometry Optimization

"Entrapped Copper(II) Carbonate For Indirect Determination Of Glycine By Flow Injection Atomic Absorption Spectrometry"
Anal. Chim. Acta 1993 Volume 274, Issue 2 Pages 275-281
J. V. Garcia Mateo, J. Mart&iacute;nez Calatayud*

Abstract: The immobilization of CuCO3 in AL-100-A polyester resin during polymerization is described. The resulting solid resin, with an optimum reagent concentration. of 1 g mL-1 and particle size 150 to 200 µm was packed into a column (13.5 cm x 0.8 mm) for use as a reactor in the cited determination of glycine; the analyte complexed with and dissolved immobilized Cu(II) which was then determined by AAS at 324.8 nm. Flow injection analysis and chemical parameters were optimized: the injection volume was 345 µL, and the Na2B4O7 - HCl - NaOH carrier buffer concentration. was 5 mM with a pH of 9.25 and a flow rate of 4.2 mL min-1. The calibration graph was rectilinear from 1.2 (detection limit) to 35 µg mL-1, the coefficient of variation (n = 20) was 1.1% at 20 µg mL-1 and the sample throughput was 180 h-1. Tolerance limits for potential interferents are given. The method was applied to glycine determination in tablets (Okal) and drinking phials (Actilevol). Results agreed with certified values.
Glycine Spectrophotometry Immobilized reagent Optimization Reference material Interferences Indirect

"Flow Injection Spectrophotometric Determination Of Amino-acids Based On An Immobilized Copper(II)-zincon System"
Anal. Chim. Acta 1993 Volume 281, Issue 3 Pages 601-605
L. Lahuerta Zamora, J. Mart&iacute;nez Calatayud

Abstract: The flow injection spectrophotometric determination of different amino acids was carried out by reaction with copper(II) ions entrapped in a polymeric material and filling a packed-bed reactor; the released copper(II), complexed with the amino acid, reacted with zincon in a basic medium producing a blue color that was monitored at 600 nm. The method was applied to determine the contents of different amino acids in pharmaceutical formulations. The calibration graph for glycine was a linear over the range 0.5-20 µg mL-11 with a relative standard deviation of 0.8% (n = 6) at 10 µg mL-1 and a sample throughput of 108 h1-1. The test solution (359 µL) was injected into a stream (2.7 ml/min) of 12.5 mM sodium tetraborate/4.6 mM HCl buffer of pH 9, which was passed through a reactor (13.5 cm x 1.5 mm i.d.; 150-200 µm) containing CuCO3.Cu(OH)2.2H2O and Co (as catalyst) entrapped in AL-100-A polyester resin (Reposa) prepared as described previously (cf. Ibid., 1992, 265, 81). The solution was then mixed with a stream (3.4 ml/min) of 0.1 mM zincon in the same buffer in a 30 cm reaction coil, and the absorbance of the released Cu(II)-zincon complex was measured at 600 nm. The calibration graph was linear from 0.5-20 µg/ml of glycine and the RSD was 0.85% (at 10 mg/ml); hourly throughput was 108 samples. Of the compounds that may be present in pharmaceuticals containing amino-acids, only ascorbic acid interfered (at 10 mg/ml of amino-acid and up to 500 mg/ml of interferent). The method was used successfully to determine glycine in phial contents and tablets, with RSD of 1 and 2.9%, respectively. The method was also applied in the determination of proline, histidine, alanine, leucine and phenylalanine (calibration data given).
Amino Acids l-Proline Histidine Alanine Leucine Phenylalanine Spectrophotometry Interferences Catalysis Solid phase reagent Resin Immobilized reagent

"Flow Injection Spectrophotometric Determination Of Tetracycline Antibiotics"
Anal. Chim. Acta 1994 Volume 285, Issue 1 Pages 9-12
R. Karlicek and P. Solich

Abstract: Tablets were dissolved in water, sedimented and filtered. Portions of the filtrate were injected into a water carrier stream (0.67 ml/min) which mixed with a reagent comprising aqueous 4-aminophenazone, di-sodium EDTA buffer of pH 10 and 1% Brij 35 at 0.54 ml/min in a coil prior to reaction with potassium hexacyanoferrate(III) (0.54 ml/min) in a second coil at ambient temperature The absorbance of the dye formed was measured at 520 nm. A modified simplex method was employed to optimize several mutually affected variables and individual variables (tabulated), including the lengths of the coils used and the concentrations of reagents. Calibration graphs (peak height) were linear (r 0.995) for 1-20 and 20-250 mg/l of doxycycline, oxytetracycline, rolitetracycline and tetracycline with RSD of 1% for 10 and 100 mg/l and an output of 60-70 samples/h.
Doxycycline Oxytetracycline Rolitetracycline Tetracycline Spectrophotometry Modified simplex Optimization

"Continuous-flow Injection Atomic Absorption Spectrometric Method For The Determination Of Ondansetron"
Anal. Chim. Acta 1995 Volume 300, Issue 1-3 Pages 143-148
L. Lahuerta Zamoraa and J. Mart&iacute;nez Calatayudb,*

Abstract: A solid-phase reactor was prepared from PbO2 entrapped by polymerization of unsaturated esters in a polyester resin. The powdered material of particle size 200-250 µm was introduced into a 1.5 mm i.d. PTFE tube and placed in a FIA continuous-flow manifold. An aqueous solution of ondansetron in H2SO4 medium was injected into a carrier stream of water and passed through the reactor at a flow rate of 5.4 ml/min. The released Pb(II) was monitored by AAS at 217 nm. The calibration graph was linear in the range 0.5-20 µg/ml of ondansetron at room temperature and, for a sample volume of 405 µL, the throughput was 338 samples/h. The RSD for 10 µg/ml of analyte at room temperature and 80°C were 2% (n = 29) and 1.8% (n = 35), respectively. The between-day reproducibility had a RSD of 2.1% and foreign compounds did not interfere. The method was applied to the analysis of tablets.
Ondansetron Spectrophotometry Solid phase reagent Interferences

"Preconcentration Of An Analyte Dialysate In A Flow Injection System"
Anal. Chim. Acta 1995 Volume 308, Issue 1-3 Pages 214-221
J. F. van Staden* and C. J. Hattingh

Abstract: An FIA system with online dialysis, pre-concentration by ion-exchange and detection by AAS was evaluated and optimized. The various functions of the system were controlled by a time regulated system from a computer. The system was used to determine Cu in vitamin and mineral food supplements for dogs and cats. A 2 g portion of the food supplement was shaken with water for 30 min and the resulting slurry was diluted to 1000 mL with ammonium acetate/ammonia buffer at pH 8.7 (buffer A). After allowing insoluble material to settle, 22 µL of the supernatant was injected into the donor stream (buffer A, 2.5 ml/min) of the FIA manifold. After passing through the dialyser unit, the acceptor stream (buffer A, 1.4 ml/min) was propelled through an Dionex OnGuard-H ion-exchange column (1.2 cm x 1.4 mm i.d.). The flow-through the ion-exchange column was reversed and the retained Cu was eluted by injecting 1 mL of eluent into the buffer stream. Cu was determined by AAS at 324.6 nm with N2O/acetylene flame. The eluent contained 1 M HCl, 1 M HNO3 and 0.1 M NaCl. The results obtained using a calibration graph covering the range 0.5-5 mg/l Cu were in agreement with manufacturers` specifications and comparable to those obtained by direct AAS measurement. The detection limit in the food supplement was 0.015% with a 2 g sample and the RSD (n =15) was 5.74%.
Copper Spectrophotometry Preconcentration Dialysis Resin Method comparison Optimization

"Determination Of Calcium In Water, Urine And Pharmaceutical Samples By Sequential Injection Analysis"
Anal. Chim. Acta 1996 Volume 323, Issue 1-3 Pages 75-85
J. F. van Staden* and R. E. Taljaard

Abstract: The sequential injection analysis is based on the fast complexation reaction between metalphthalein and Ca2+ followed by spectrophotometric detection at 573 nm. Plugs of 0.31 mL of water, 0.47 mL of 14% 2-amino-2-methylpropanol-1-ol buffer solution of pH 10.5, 0.23 mL of 0.0025% metalphthalein solution of pH 1.9 and 0.23 mL of sample were drawn at 4.68 ml/min into a holding coil (50 cm x 1.6 mm i.d.). The flow was then reversed and the stacked plugs were propelled through reaction coils (90 cm x 1.1 mm i.d. and 115 cm x 0.6 mm i.d.) to the flow-though detection cell (80 µL) where the absorbance was measured. A linear response was obtained for up to 20 mg/l of Ca and the detection limit was 0.05 mg/l. The RSD (n = 10) for 1-20 mg/l Ca were 0.66-0.85%. The method was applied to the determination of Ca in an effervescent tablet, tap water and urine, and the results were validated by AAS. The sampling frequency was 43 per h.
Calcium Spectrophotometry Sequential injection

"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

"Photocured Polymers In Ion-selective Electrode Membranes. 6. Photopolymerized Lithium Sensitive Ion-selective Electrodes For Flow Injection Potentiometry"
Anal. Chim. Acta 1996 Volume 335, Issue 1-2 Pages 111-116
J. R. Farrell, P. J. Iles,* and T. Dimitrakopoulos

Abstract: Li ISE were prepared using the ionophore, NN-dicyclohexyl-N'N'-di-isobutyl-cis- cyclohexane-1,2-dicarboxamide (ETH 1810). A mixture of Ebecryl 600 (an aromatic epoxyacrylate), 1,6-hexanedioldiacrylate, didecylphthalate, Uvecryl P36 (a copolymerizable benzophenone photoinitiator), ETH 1810 and potassium tetrakis(p-chlorophenyl)borate was prepared and deposited on the Cu substrate of a solid contact electrode. The polymerization was carried out by exposure to a high-intensity medium pressure Hg vapor lamp for 40 min under N2. The cured electrode was conditioned in 0.1 M LiCl for 2 days. In batch-type experiments with pure LiCl solutions the electrode exhibited a hyper-Nernstian slope of 62 mV per activity decade, a log-linear range for 0.1-100 mM and a detection limit of 70 µM. The response of the electrode was independent of pH between 2 and 11 and the response time was In flow injection potentiometric experiments with 0.05 M NaCl as the carrier (1.6 ml/min) and an injection volume of 100 µl, the response slope was 49 mV per activity decade, the log-linear range was 1-100 mM, the detection limit was 0.5 mM and the sample throughput was 150/h. The FIA system was used to determine Li in lithium carbonate tablets. The selectivity of the electrode was not sufficient for the determination of Li in human blood.
Lithium Electrode Potentiometry Electrode Detector

"Determination Of Ascorbic Acid In A Mixture Of Ascorbic Acid And Uric Acid At A Chemically Modified Electrode"
Anal. Chim. Acta 1997 Volume 343, Issue 1-2 Pages 49-57
Zhiqiang Gao*, Kok Siong Siow, Adeline Ng and Yimin Zhang

Abstract: The electrochemical behaviours of ascorbic acid (AA) and uric acid (UA) at a vitreous C electrode modified with 3,4-dihydroxybenzaldehyde were investigated by voltammetry and amperometry. At pH 7.4, the anodic peak due to the oxidation of AA occurred at 0.15 V (vs. SCE) at the modified electrode, which was at least 250 mV more negative than the voltage required at an unmodified electrode. The modification of the electrode had no effect on the oxidation of UA. The modified electrode was employed in a flow injection system for the amperometric determination of AA in the presence of UA. A thin layer flow-through electrochemical cell was used equipped with the working electrode maintained at 0.15 V, a SCE as the reference electrode and a Pt foil counter electrode. The carrier stream (1 ml/min) was 0.1 M phosphate buffer at pH 7.4. A linear response was obtained for 0.7 µM- to 1 mM AA, the detection limit was 0.3 µM and the RSD (n = 50) for 10 µM-AA was 4%. The system was used to determine AA in single- and multi-vitamin tablets.
Ascorbic acid Uric acid Amperometry Voltammetry Electrode Electrode Detection limit Selectivity

"Determination Of Acetaminophen By Flow Injection With Online Chemical Derivatization. Investigations Using Visible And FTIR Spectrophotometry"
Anal. Chim. Acta 1998 Volume 364, Issue 1-3 Pages 107-116
Maiella L. Ramos, Julian F. Tyson and David J. Curran*

Abstract: A new FI/FTIR method for the determination of acetaminophen involving online reaction was based on the alkaline hydrolysis of the analyte to produce p-aminophenol and its oxidation reaction with potassium ferricyanide to produce p-benzoquinone-monoimine which eventually oxidized to form p-benzoquinone. The chemical of the reaction was studied both, in the visible and IR regions of the spectrum and the method was developed by the application of flow injection methodology The reaction was carried out in aqueous media and at room temperature The micro-flow version of the CIRCLE IR accessory, which is compatible with aqueous solutions, was used. Measurements were carried out at the OH-phenolic deformation (1274.1 cm-1) and the arom. ring mode (1498.2 cm-1) IR vibrations for the hydrolysis product, p-aminophenol. The method was applied to the determination of acetaminophen in commercial tablets, and mean detection values of 512 and 491 mg were found at 1274.1 and 1498.2 cm-1, respectively.
Acetaminophen Spectrophotometry Spectrophotometry CIRCLE cell

"Automated Flow Injection System For Extending The Linear Range"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 271-279
Luis F. Gouveia, Jos&eacute; L. F. Costa Limab and Jos&eacute; A. G. Moraisa,*

Abstract: A flow system with built-in capability to adjust injection volume whenever sample concentration. is higher than the upper linearity limit was developed and its performance assessed. Solenoid valves were used to manage sample and carrier delivery. Whenever the peak height is higher than the calculated linearity limit an injection volume adjustment is made to a 2nd determination of the same sample in such a way that the peak height will be in the linear range. Extended linear range is therefore achieved without sacrificing detection of low concentration. samples. Calibration, calculation of the upper linearity limit and model fitting to calibration data (peak height vs. concentration. and peak height vs. injection volume) are automatically performed with no human intervention. Performance was tested upon assessing dissolution profiles of cephalexin tablets in a low dispersion manifold with direct UV determination The proposed system presents a 180 determinations h-1 throughput. Sample aspiration time was calibrated in the range 50-2000 ms, thus allowing quantification up to 1250 mg L-1 of cephalexin. Precision is ~0.95% relative standard deviation when sample is aspirated for 2000 ms. Results obtained are comparable to those obtained by using the reference procedure.
Cephalexin Spectrophotometry Linear dynamic range Automation Computer Method comparison Standard method Dissolution rate

"Automatic Multicommutation Flow System For Wide Range Spectrophotometric Calcium Determination"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 45-53
F&aacute;bio R. P. Rocha, Patr&iacute;cia B. Martelli, Rejane M. Frizzarin and Boaventura F. Reis*

Abstract: An automatic flow system based on multicommutation concept is proposed to widen the linear concentration range for spectrophotometric calcium determination The flow network was build up with three way solenoid valves to permit implementation of different sample processing conditions to achieve limited, medium and large dispersion degree without modification of the manifold configuration. Dilutions were carried out by changing both sampled volume and the analysis path length or applying zone sampling approach. The software was developed to control all steps of sample processing and to allow changing the manifold configuration to obtain suitable sample dilution This condition was attained with up to 3 trials. A linear response from 0.250 to 1000 mg L-1, and a detection limit of 7 µg L-1 (99.7% confidence level) were achieved. The relative standard deviation was 0.83% (n = 10) or better. The sampling rate was ~60 h-1 and 0.27 µg of the chromogenic reagent (3,3'-bis[N,N-bis(carboxymethyl)aminomethyl]-o-cresolphthalein) was consumed per determination The procedure was applied to calcium determination in waters, plant materials, milk, antacid tablets, fertilizers and calcareous rocks. The results were in agreement with certified values or with those obtained with flame atomic absorption spectrophotometry at a 95% confidence level.
Calcium Spectrophotometry Automation Commutation Method comparison Reference material Valve Dilution

"Acetylsalicylic Acid Determination In Pharmaceutical Samples By FIA-potentiometry Using A Salicylate-sensitive Tubular Electrode With An Ethylene-vinyl Acetate Membrane"
Anal. Chim. Acta 1998 Volume 366, Issue 1-3 Pages 103-109
La&eacute;rcio Rover Jr., Carlos Alexandre Borges Garcia, Graciliano de Oliveira Neto*, Lauro Tatsuo Kubota and Fernando Galembeck

Abstract: The preparation of a salicylate-sensitive tubular potentiometric electrode for flow injection analysis (FIA) is described. An ethylene-vinyl acetate (EVA) copolymeric membrane (40% vinyl acetate) was applied directly onto a conducting support of epoxy resin/graphite mixture. The tubular salicylate ion-selective electrode was based on tricaprylyl trimethylammonium (Aliquat)/salicylate as the ion exchanger supported by the polymeric matrix without a plasticizer solvent. The tubular electrode showed a response of 58.3 mV per concentration decade within the 5.0 x 10^-3 to 5.0 x 10^-1 M salicylate range in 0.1 M Tris-HCl buffer pH 7.5. Iodide was the main anal. interferent. The electrode response time was 5 s at 25°C. Acetylsalicylic acid in tablets was hydrolyzed with NaOH before FIA determination. Determinations of acetylsalicylic acid in tablets by the proposed method showed relative errors <2%, when compared with a standard spectrophotometric method. The useful lifetime of the tubular sensor is >3 months.
Acetylsalicylic acid Electrode Electrode Potentiometry Electrode Interferences Method comparison

"Combination Of Flow Injection With Capillary Electrophoresis. 4. Automated Multicomponent Monitoring Of Drug Dissolution"
Anal. Chim. Acta 1998 Volume 376, Issue 2 Pages 209-220
Heng-Wu Chen and Zhao-Lun Fang*

Abstract: The combined flow injection-capillary electrophoresis (FI-CE) system, described previously in this series, was used in connection with a drug dissolution testing system to automatically monitor the dissolution process of multicomponents. Samples from the dissolution medium were withdrawn at fixed intervals through an online membrane filter to load the sample loop of an injection valve, from which 25 µL samples were injected into a carrier buffer and transported into a split-flow interface coupling the FI and CE systems. Trimethoprim (TMP) and sulfamethoxazole (SMZ), the two active components in a sulfatrim tablet formulation dissolved in 0.1 mol L-1 HCl, were introduced into a short silica separation capillary of 14.5 cm effective length by electrokinetic means, separated at a constant voltage of 1.0 kV by capillary zone electrophoresis, using a phosphate running buffer (pH 6.5), and the separated constituents recorded continuously, using an UV detector at 224 nm. The signals were recorded within a testing period of 65 min. By partially overlapping the separation zones of neighboring samples, a high sample throughput of 60 h-1 was achieved with single-vessel dissolution and 48 (24 duplicates) h-1 with dual-vessel dissolution The reproducibility of the FI-CE system, obtained using TMP and SMZ standards within the testing period was 1.6 and 0.8% relative standard deviation (RSD) with peak height evaluation, and 2.0 and 1.1% RSD (n=72), respectively, for peak area. Good agreement of results was obtained between those using the reported method and a standard liquid chromatography method.
Trimethoprim Sulfamethoxazole Electrophoresis Method comparison Dissolution rate Interface

"Flow Injection Determination Of Ergonovine Maleate With Amperometric Detection At The Kel-F-graphite Composite Electrode"
Talanta 1986 Volume 33, Issue 5 Pages 448-450
F. Belal* and J. L. Anderson

Abstract: Tablets containing ergometrine maleate(I) were powdered and dissolved in the mobile phase [methanol - 0.01 M phosphate buffer - 2% Na acetate (pH 7) (1:4)] and subjected to flow injection analysis with amperometric detection with a Kel-F - graphite electrode at +0.85 V vs. silver - AgCl. The calibration graph was rectilinear for 1 to 20 µg mL-1 of I and the detection limit was 50 ng mL-1. The coefficient of variation were 1%, and the results agreed well with those obtained by the official USP method.
Drugs Ergometrine maleate Amperometry Electrode Method comparison

"Flow Injection Colorimetric Method For The Assay Of Vitamin C In Drug Formulations Using Tris-(1,10-phenanthroline)iron(III) Complex As An Oxidant In Sulfuric Acid Media"
Talanta 1994 Volume 41, Issue 1 Pages 125-130
Salah M. Sultan, Abdella M. Abdennabi and Fakhr Eldin O. Suliman

Abstract: Powdered tablets were dissolved in water and treated with H2SO4. Portions (110 µL) of the solution were injected into 0.01 M Fe(III) in a 0.05 M H2SO4 carrier stream which was pumped through PVC tubing after merging with 0.25% 1,10-phenanthroline in 0.05 M H2SO4. The reactants were mixed in a PTFE reaction coil (45 cm x 0.5 mm i.d.) prior to transport through a micro-flow cell (20 µL) with a 1 mm path length and the absorbance was measured at 510 nm. The calibration graph was linear for 50-400 ppm of vitamin C (ascorbic acid; I). A sample throughput of 100/h was obtained for 100-400 ppm of I with a RSD of 0.9%. Good agreement was observed for the I content of proprietary drugs measured by FIA and by the B.P. method. Glucose, starch and carbonate did not interfere.
Ascorbic acid Spectrophotometry Interferences

"Amperometric Enzyme Electrodes For The Determination Of L-glutamate"
Talanta 1991 Volume 38, Issue 1 Pages 49-56
Rhodora L. Villarta, David D. Cunningham, and George G. Guilbault

Abstract: Electrodes for amperometric measurement of L-glutamate were prepared by immobilization of L-glutamate oxidase on an Immobilon-AV Affinity membrane and attachment to an oxygen/hydrogen peroxide sensor. The response of the hydrogen peroxide sensor was linear over the concentration range 5.0 times 10^-8-5.0 times 10^-4 M L-glutamate, with a limit of detection of 35 nM. Attachment of a size-exclusion membrane (cut-off for molecular weight gt 100) or of a hydrophobic oxygen membrane eliminated electro-oxidizable interferences, but the response was attenuated by a factor of 2-3. The response may be amplified 10-fold by co-immobilizing L-glutamate dehydrogenase with the L-glutamate oxidase. The electrode initially lost 25% of its activity but was then stable for more than 320 days and at least 200 assays. The electrode was successfully used to assay glutamate in a protein tablet and in several food products. A flow injection system was assembled for the continuous assay of L-glutamate.
l-Glutamate Amperometry Apparatus Membrane Interferences

"Flow Injection Fluorimetric Determination Of Trimeprazine And Trifluoperazine In Pharmaceutical Preparations"
Talanta 1993 Volume 40, Issue 9 Pages 1361-1365
T. P&eacute;rez-Ruiz*, C. Mart&iacute;nez-Lozano, V. Tom&aacute;s and C. Sidrach de Cardona,

Abstract: The flow injection system described is based on the oxidation of trimeprazine (I) and trifluoperazine (II) by Ce(IV) and the fluorimetric determination of Ce(III). Finely ground tablets were extracted by water with ultrasonic mixing and the resulting suspension was filtered. A 158 µL portion of the filtrate was injected into a stream (0.8 ml/min) of 1 mM Ce(IV) in 1 M H2SO4 at 30°C. After passing through the reaction coil (30 cm x 0.5 mm) the Ce(III) was detected fluorimetrically at 355 nm (excitation at 255 nm). The calibration graphs were rectilinear for 0.2-10 µM-I and II with RSD (n = 10) of 0.8-1.2% with a recovery of 96-104%. The sampling rate was 60 samples/h. The tolerance limits for various foreign substances are listed. Ascorbic acid, acetylsalicylic acid and Na2SO3 interfere.
Trimeprazine Trifluoperazine Cerium(3+) Fluorescence Interferences Heated reaction

"Simultaneous Determination Of Acetylsalicylic Acid And Caffeine In Pharmaceuticals By Flow Injection With Fourier Transform Infrared Detection"
Talanta 1993 Volume 40, Issue 12 Pages 1799-1807
Salvador Garrigues, M&aacute;ximo G&aacute;llignani and Miguel de la Guardia

Abstract: Samples were extracted with CH2Cl2 to give a final concentration of 10 mg/ml of acetylsalicyclic acid (aspirin; I) and 1 mg/ml of caffeine (II). The solution were filtered or centrifuged and introduced as the carrier stream (0.81 ml/min) into a 5 µL flow cell. I was measured at 1770 cm-1 and II at 1661 cm-1, with a common baseline between 1900 and 1537 cm-1. Two standard solution containing 90% and 110% of the expected I and II concentrations, respectively, were injected into the sample carrier stream and also measured; the I and II concentrations were found by interpolation. There was a small effect of I on the determination of II ; this was overcome by using II standards containing the expected concentration of I. Stopped-flow methods, with use of calibration graphs, could also be used, but the reversed-flow method described was quicker. Results are presented for six brands of tablets.
Aspirin Caffeine Spectrophotometry Stopped-flow Reverse

"Sequential Optimization Of A Flow Injection Spectrophotometric Method For The Assay Of Chlorpromazine In Pharmaceutical Preparations"
Talanta 1994 Volume 41, Issue 11 Pages 1865-1871
Fakhr Eldin, O. Suliman and Salah M. Sultan

Abstract: A previously describer FIA system (Sultan, Analyst (London), 1991, 116, 177) was used for the analysis of chlorpromazine. Powdered tablets equivalent to 500 ppm chlorpromazine were dissolved in water, heated in a water bath for 20 min, filtered and the filtrate injected into a carrier stream of 3.8 mM cerium (IV) in 35 mM H2SO4 (4.85 ml/min). After passing through a reaction coil (45 cm x 0.5 mm i.d.) a color developed which was measured spectrophotometrically at 525 nm. Calibration graphs were linear for 50-200 ppm chlorpromazine with RSD (n = 5) of 0.7%. Recoveries from commercial tablets were 98.74-100.9% which agreed well with results obtained by the B.P. method.
Chlorpromazine Spectrophotometry Optimization

"Flow Injection Fluorimetric Analysis Of Sulfamethoxazole In Pharmaceutical Preparations And Biological Fluids"
Talanta 1994 Volume 41, Issue 12 Pages 2159-2164
C. Lopez Erroz, P. Vi&ntilde;as and M. Hern&aacute;ndez C&oacute;rdoba*,

Abstract: Pharmaceuticals were dissolved in ethanol and filtered, and urine and serum were diluted with water and filtered. The filtrate was injected into a stream of 0.01 M o-phthaldialdehyde in 0.7 M H3PO4 and merged with a stream of 0.01 M β-mercaptoethanol in 0.7 M H3PO4. The resulting solution flowed through a reactor coil (2.5 m x 0.5 mm i.d.) thermostatted at 40°C and into a flow cell for fluorimetric detection at 412 nm (excitation at 302 nm). The system flow rate was 1 ml/min. The calibration graph was linear for 0.01-2.5 µg/ml of sulfamethoxazole with a detection limit of 7 ng/ml. The RSD (n = 10) were 3.5, 2.2 and 2.1% for 0.01, 0.05 and 1.5 µg/ml, respectively. Interferences from tablet fillers and other compounds are discussed.
Sulfamethoxazole Fluorescence Interferences

"FIA Spectrophotometric Determination Of Thiamine After UV-irradiation"
Talanta 1994 Volume 41, Issue 12 Pages 2147-2151
Andrei F. Danet* and J. Martinez Calatayud

Abstract: The estimation of thiamin was carried out by UV-photodegradation in a single-line flow injection assembly. The UV-photodegradation of thiamin was carried out in the coil of the injection valve, constituted of a PTFE tubing, half of its length being helically coiled around a UV lamp. A peak with 2 adjoining maxima was produced by injection, corresponding to the absorbance of the irradiated and non-irradiated sample. The analytical parameter is the difference between the 2 peaks, estimated at 264 nm. The calibration graph is linear over the 1.2-30 µg/ml range of thiamin hydrochloride in 0.1 M HCl. The influence of certain admixed substances was studied and the method was tested for the estimation of thiamine in tablets.
Thiamine Spectrophotometry Photochemistry UV reactor

"Flow Analysis-spectrophotometric Determination Of L-dopa In Pharmaceutical Formulations By Reaction With P-aminophenol"
Talanta 1995 Volume 42, Issue 4 Pages 627-633
Berween A. Hasan, Karim D. Khalaf and Miguel De La Guardia*

Abstract: The method is based on the reaction between dopa in NaOH and p-aminophenol (PAP). One procedure was in stopped-flow mode and another was a flow injection approach (diagrams given). In the stopped-flow mode, three channels, contained 0.2 M NaOH, 100 µg/ml PAP and the sample (ground solid formulations, dissolved in water and filtered). After mixing, the spectrophotometric measurements were carried out at 574 nm after 1 min. In the FIA mode, the samples were injected using 600 µL injection volume and distilled water as carrier stream (3.2 ml/min). The calibration graph was linear from 2-8 µg/ml and the detection limit was 52 ng/ml. RSD were 0.2% (n = 3) and recoveries were 97.7-101.5%.
l-Dopa Spectrophotometry Stopped-flow

"FIA-spectrophotometric Determination Of N-substituted Phenothiazine Derivatives By Oxidation With A Solid-phase Reactor Of Manganese Dioxide Incorporated In Polyester Resin Beads"
Talanta 1995 Volume 42, Issue 7 Pages 909-913
A. Kojlo,* and J. Martinez Calatayud

Abstract: The bed-reactor was prepared with 11.81 g MnO2 homogenized with 15.74 g Al-100-A polyester resin solution (Reposa, Valencia, Spain) followed by addition of methyl ethyl ketone as catalyst. The resultant solid was reduced to small particles. Those measuring 300-400 µm were washed and introduced into PTFE tubing by suction. A diagram of the flow injection manifold is presented. Optimization of FIA parameters was carried out by the univariate method. For all drugs (promazine, promethazine, thioridazine and chloropromazine hydrochlorides, diethazine maleate and trifluoriperazine) the sample volume was 612 µL and the carrier (H2O) flow rate was 3.2 ml/min. For all drugs except thioridazine HCl, the length of the column was 170 cm, and the concentration of HCl (merged with sample in carrier stream before entering reactor) was 1 M and detection wavelength was 500-526 nm. Corresponding parameters for thioridazine were 120 cm, 0.5 M and 634 nm. The calibration graph was linear from 5-50 µg/ml, with RSD of 0.5-1%. The sample throughput was 40-48/h. The effect of foreign compounds is tabulated. Determination of the drugs in tablets was carried out by dissolving powdered tablets in methanol, filtering, evaporating to dryness and dissolving the residue in H2O.
Phenothiazine, derivatives Chlorpromazine, hydrochloride Diethazine maleate Promazine Promethazine Thioridazine hydrochloride Trifluperazine Spectrophotometry Resin Interferences Optimization Reactor

"Determination Of Hydrazine Derivatives By Flow Injection Analysis With Spectrophotometric Detection"
Talanta 1995 Volume 42, Issue 10 Pages 1465-1469
M. I. Evgen'ev, S. Y. Garmonova, I. I. Evgen'eva and H. C. Budnikov

Abstract: A diagram is presented of a flow injection manifold used in the spectrophotometric determination of hydrazine-based drugs. The method was based on the reaction of 4-chloro-5,7-dinitrobenzofurazan (DNBF) with the hydrazine derivatives. The 0.02 M DNBF acetonitrile solution was injected directly into a carrier solution of the hydrazine derivatives (concentration range 0.15-4 µg/ml) and the absorbance at 510 nm was measured. For the determination of 1-hydrazinophthalazine hydrochloride in apressin drug, powdered tablets containing ~10 mg of the drug were diluted to 100 mL with water. The mixture was shaken, filtered and a 5 mL portion was diluted to obtain a final solution containing ~1 µg/ml drug. For the determination of hydrazine drugs in plasma, urine and albumin, 1 mL TCA was added to 4 mL sample followed by centrifugation at 6000 rpm. The supernatant was neutralised with 0.5 mL acetate buffer of pH 5.5 and analyzed by the above procedure. The calibration graphs were linear from 0.15-4 µg/ml, with sampling rates of 28-32/h. Interferences from other compounds are tabulated. Flow injection analysis for the determination of hydrazine derivatives based on their nucleophilic substitution reaction with 4-chloro-5,7-dinitrobenzofurazan in aqueous medium, and spectrophotometric detection has been described. The calibration graphs were linear in the range from 0.15 to 4.0 µg mL-1 of hydrazine derivatives, with sampling rates of up to 28-32 samples h-1. Interferences from amino compounds, benzoic acids, aliphatic amines and ammonia have been evaluated. The procedure has been applied to the determination of hydrazine derivatives in serum, urine, apressin drugs and artificial mixtures. (16 references)
Drugs Hydrazine Spectrophotometry Interface Interferences

"Chemiluminescent Determination Of Pyridoxine Hydrochloride In Pharmaceutical Samples Using Flow Injection"
Talanta 1998 Volume 45, Issue 6 Pages 1131-1138
Abdulrahman A. Alwarthan* and Fatima A. Aly

Abstract: A chemiluminescent method using flow injection is described for the determination of pyridoxine. Its detection limit, linearity and reproducibility were examined The method was based on the enhancing effect of pyridoxine on the chemiluminescence generated by the oxidation of luminol with hydrogen peroxide in aqueous potassium hydroxide and sodium oxalate. The proposed method is simple and inexpensive. The chemiluminescence intensity is a linear function of pyridoxine concentration. over the range 10^-250 µg mL-1 with a detection limit of 6 µg mL-1. The applicability of the method was demonstrated by the determination of pyridoxine in different tablets and some dietary sources.
Pyridoxine Chemiluminescence Indirect

"Cerium(IV)-based Chemiluminescence Analysis Of Hydrochlorothiazide"
Talanta 1998 Volume 46, Issue 5 Pages 961-968
J. Ouyang, W. R. G. Baeyens*, J. Delanghe, G. Van der weken and A. C. Calokerinos

Abstract: A flow injection analysis method for the determination of hydrochlorothiazide is presented. The method is based on the chemiluminescence reaction of hydrochlorothiazide with cerium(IV) in sulfuric acid, sensitized by the fluorescent dye rhodamine 6G. The proposed procedure allows quantitation of hydrochlorothiazide in the concentration. range of 0.33-130 µmol L-1 with a detection limit of 0.15 µmol L-1, an relative standard deviation of 2.4% at 10 µmol L-1 and a sample measurement frequency of 200 h-1. The method was successfully applied to the determination of hydrochlorothiazide in pharmaceutical preparations containing, amongst others, lactose, maize starch, calcium phosphate, magnesium stearate, potassium chloride and E 110 (disodium-6-hydroxy-5-(4-sulfonatophenylazo) naphthalene-2-sulfonate) as the concomitant species. Apart from the single formulation, hydrochlorothiazide was also determined in tablets combined with the antihypertensive lisinopril.
Hydrochlorothiazide Chemiluminescence Indirect

"Determination Of Readily Oxidized Compounds By Flow Injection Analysis And Redox Potential Detection"
Analyst 1978 Volume 103, Issue 1232 Pages 1154-1159
Bo Karlberg and Sidsel Thelander

Abstract: Reducing agents injected into a nonsegmented stream of Ce(IV) solution and were determined by measuring the ratio of Ce(III) to Ce(IV) with suitably placed graphite or Pt electrodes and suitably placed indicator and reference electrodes. Electrodes were made of Pt tube and wire and of graphite as the core in a PTFE tube. Well defined peaks were obtained with 0.3 mL samples and reagent flow rates of 0.7-1.0 mL/min. Ascorbic acid and Fe(II) ≤1 mM in aqueous solution were determined with good reproducibility at a sample rate ~45-60/h. The relative standard deviation for the determination of ascorbic acid in C-vimin tablets containing 1 g active component was 1.2%.
Ascorbic acid Iron Electrode Electrode Potentiometry Automation Redox

"Automated Flow Injection Spectrophotometric Determination Of Some Phenothiazines Using Iron Perchlorate: Applications In Drug Assays, Content Uniformity, And Dissolution Studies"
Analyst 1986 Volume 111, Issue 3 Pages 313-318
Michael A. Koupparis and Antonie Barcuchov&aacute;

Abstract: Solutions (200 µL) of pharmaceutical formulations containing a phenothiazine were fed at 2.4 mL min-1 into an automated flow injection analysis system with 2.75 mM Fe(ClO4)3 - 10 M HClO4 solution as oxidizing agent and water as carrier solution. The products were passed to a spectrophotometer set at the λmax of the individual drug. Chlorpromazine, promethazine, promazine, methotrimeprazine, thioproperazine, fluphenazine, trifluoperazine and thioridazine were determined in the range 10 to 250 µg mL-1. The precision was better than 1% and a measurement rate of 120 h-1 could be attained. The method was evaluated by studying interference effects and recoveries and by the analysis of commercial formulations, the results of which were compared with those from the official USP method. The technique was used in content uniformity tests and for monitoring the dissolution of solid dosage forms in 0.1 M HCl.
Chlorpromazine Promethazine Promazine Methotrimeprazine Thioproperazine Fluphenazine Spectrophotometry Interferences Review

"Determination Of Nitrazepam And Flunitrazepam By Flow Injection Analysis Using A Voltammetric Detector"
Analyst 1987 Volume 112, Issue 5 Pages 697-699
Elisa Ruiz, Manuel Hern&aacute;ndez Blanco, Encarna Lorenzo Abad and Lucas Hern&aacute;ndez

Abstract: Sample solution (200 µL), containing 5.6 to 28.1 µg mL-1 of nitrazepam(I) or 6.3 to 31.3 µg mL-1 of flunitrazepam(II), was injected into a carrier stream of 0.1 M phosphate buffer (pH 7.0) containing 10% of methanol. I and II were determined by reduction at a vitreous-carbon electrode at -0.9 V vs. silver - AgCl - KCl. A reaction coil (70 cm x 0.5 mm) was incorporated before the detector. The flow rate was 4 mL min-1 and the sampling frequency was 100 h-1. The detection limits were 1.8 and 1.3 µg mL-1 for I and II, respectively. The procedure was used to determine 5 mg of I and 2 mg of II in tablets.
Nitrazepam Flunitrazepam Electrode Voltammetry Apparatus

"Application Of A Photodiode Array Detector To Multicomponent Determination By Flow Injection Analysis"
Analyst 1987 Volume 112, Issue 5 Pages 619-622
Marcelo Blanco, Jordi Gen&eacute;, Hortensia Iturriaga and Santiago Maspoch

Abstract: The simultaneous determination of compounds in two-, three- and four-component mixtures with completely overlapping spectra (e.g., etafedrine, phenylephrine, doxylamine and theophylline) was achieved by flow injection analysis with a diode-array spectrophotometric detection system. The effect of wavelength range and mode of spectral selection was studied. The absorbance spectrum of each solution was recorded 10.7 s after sample injection with an integration time of 0.4 s. The method was applied in the determination of the four active components in Nethaprin tablets, with use of third-derivative spectra in the range 214 to 290 nm.
Phenylephrine Doxylamine Theophylline Etafedrine Spectrophotometry Multicomponent Simultaneous analysis

"Reductive Amperometric Determination Of Nitrofurantoin And Acetazolamide At A Sessile Mercury Drop Electrode Using Flow Injection Analysis"
Analyst 1988 Volume 113, Issue 5 Pages 727-730
Arnold G. Fogg and Ahmed B. Ghawji

Abstract: Nitrofurantoin was determined at -0.70 V vs. SCE in a carrier stream (7 mL min-1) of Britton - Robinson buffer (pH 7.5) containing 1 g L-1 of Na2SO3. The response was rectilinear from 1 to 50 ppm, with a limit of detection of 0.3 ppm and a coefficient of variation (n = 10) of 1.9% for 10 ppm. Acetazolamide was determined at -0.85 V in 0.1 M HCl. The response was rectilinear from 10 to 70 ppm, with a limit of detection of 7 ppm and a coefficient of variation (n = 10) of 2.3% for 10 ppm. In the analysis of aqueous extracts of tablets, the coefficient of variation (n = 3) were <1.0%.
Acetazolamide Drugs Nitrofurantoin Amperometry Electrode Polarography

"Flow Injection Determination Of Drugs By Specific Detection Of Carboxylic Acids"
Analyst 1988 Volume 113, Issue 11 Pages 1673-1675
Toshifumi Takeuchi, Yozo Kabasawa, Rikizo Horikawa and Takenori Tanimura

Abstract: A variety of carboxylic acid drugs were determined. A portion, containing ~0.25 mmol of drug, of the powder obtained from 20 tablets or capsules was extracted with ethanol or water, the extract was filtered, and the filtrate was analyzed in a flow injection system in which it was treated with 0.02 M 2-nitrophenylhydrazine in 0.2 M HCl and 0.05 M 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide in ethanolic 4% pyridine in the first reaction coil (10 m x 0.5 mm) at 60°C and with 1.5 M NaOH in a second coil of the same dimensions and temperature After cooling to 30°C in a third coil (1 m x 0.5 mm) the absorbance was measured at 540 nm. Satisfactory results were obtained for aspirin, ibuprofen, dehydrocholic acid, nicotinic acid and tranexamic acid, with recoveries of 99.9 to 103.4% and coefficient of variation (n = 10) of 0.8%.
Drugs Aspirin Ibuprofen Dehydrocholic acid Nicotinic acid Tranexamic acid Spectrophotometry Heated reaction

"Continuous-flow Chemiluminescence Determination Of Acetaminophen [paracetamol] By Reduction Of Cerium(IV)"
Analyst 1989 Volume 114, Issue 6 Pages 711-714
Ioanna I. Koukli, Antony C. Calokerinos and Themistocles P. Hadjiioannou

Abstract: The continuous-flow chemiluminescence analyzer described previously (Ibid., 1988, 113, 603) was applied in the determination of paracetamol with Ce(IV). Ground tablets (>20) were shaken with water for 15 min, the solution was filtered, and a portion of filtrate was analyzed under optimized conditions (loc. cit.), with 25 mM Ce(IV) in 4 M HClO4 as reductant. The calibration graph was rectilinear for 1 to 10 µg mL-1 of paracetamol and the detection limit was 0.07 µg mL-1. The coefficient of variation (n = 7) for 1 and 10 µg mL-1 were 0.7 and 0.2%, respectively. Glucose, lactose, galactose, citric acid, sodium citrate, glucitol and propane-1,2-diol interfered. Interference from most drugs could be reduced by dilution. The mean recovery of paracetamol from formulations was 101.3%. Results agreed with those obtained by a reference method.
Acetaminophen Chemiluminescence Interferences Optimization Method comparison Standard method

"Flow Injection With Anodic Polarographic Detection For The Determination Of Allopurinol In Pharmaceutical Formulations"
Analyst 1989 Volume 114, Issue 11 Pages 1449-1452
Tommaso R. I. Cataldi, Francesco Palmisano and Pier Giorgio Zambonin

Abstract: Powdered tablets (50 mg) were dissolved in 1 mM NaOH with sonication, and portions were injected into a stream (1 mL min-1) of 50 mM borate buffer (pH 9.2) for flow injection analysis, with use of a PAR model 174A polarographic analyzer., a dropping mercury electrode (0.5-s drop time) and detection at +150 mV vs. Ag - AgCl. The calibration graph was rectilinear for 300 µM, and the limit of detection was 1.8 µM. The within-run coefficient of variation (n = 10) was 3.1% for 28 µM. Mean recovery was 99.6% of the label claim. About 90 samples h-1 could be analyzed.
Allopurinol Electrode Polarography Buffer Calibration Detection limit

"Automated Flow Injection Spectrophotometric Determination Of Para- And Meta-substituted Phenols Of Pharmaceutical Interest Based On Their Oxidative Condensation With 1-nitroso-2-naphthol"
Analyst 1990 Volume 115, Issue 3 Pages 309-313
Constantinos A. Georgiou and Michael A. Koupparis

Abstract: The reaction of para- and meta-substituted phenols with 1-nitroso-2-naphthol in the presence of either Ce(IV) or Pb(IV) as an oxidant has been used to develop a fast automated flow injection (Fl) method. A stopped-flow kinetic study of the reaction revealed the optimum conditions for the proposed Fl method. Acetaminophen, amoxicillin, cefadroxil, isoxsuprine, nylidrin, propylparaben, tyrosine and metaraminol can be determined in the range 1 x 10^-4-8 x 10^-4 M, with relative standard deviations of less than 2%, and a measurement throughput of 40 measurements h-1. The method was evaluated by performing interference studies of common excipients and assaying commercial formulations of acetaminophen and isoxsuprine. The results were in good agreement with those obtained by acceptable spectrophotometric or high performance liquid chromatographic methods (mean difference 2.1%). The high sample throughput of the Fl method was exploited by performing a content uniformity test of isoxsuprine tablets. Aqueous solution of tablet or liquid formulations were passed through a 200 µL sample loop of a flow injection analyzer. and mixed with 2 mM 1-nitroso-2-naphthol in 10% DMSO - 1% polysorbate 80, the mixture was treated with 6 mM Ce(IV) in 1 M H2SO4 or 10 mM Pb(IV) in 2 M HCl and absorbance was measured at 540 or 510 nm for Ce(IV) or Pb(IV) oxidants, respectively. Calibration graphs of paracetamol, amoxycillin, cefadroxil, isoxsuprine, buphenine, propyl hydroxybenzoate, tyrosine and metaraminol were rectilinear from 10 to 80 mM in the test solution Recoveries were good and the coefficient of variation were 2%. Interference from common excipients was not significant and results agreed well with those by spectrophotometry or HPLC.
Acetaminophen Amoxycillin Cefadroxil Isoxsuprine Buphenine Tyrosine Metaraminol Nylidrin Propylparaben HPLC Spectrophotometry Interferences Calibration Stopped-flow Method comparison

"Determination Of Diphenhydramine Hydrochloride By Flow Injection With Bromophenol Blue And Turbidimetric Measurement"
Analyst 1990 Volume 115, Issue 6 Pages 855-858
J. Martinez Calatayud, A. Sanchez Sampedro and S. Navasquillo Sarrion

Abstract: Powdered tablets were mixed with water, the mixture was filtered and diluted to volume A 210 µL aliquot of the solution was injected into a carrier - reagent stream (2.69 mL min-1) of 1.19 mM bromophenol blue (pH adjusted to 1.2 with HCl). The turbidity was measured spectrophotometrically at 650 nm. The calibration graph was rectilinear for 50 to 230 ppm of diphenhydramine hydrochloride. The coefficient of variation (n = 20) was 0.3% and the injection rate was 51 samples h-1. The study of a number of diphenhydramine-dye systems was carried out in order to determine the most suitable precipitate for the turbidimetric determination of diphenhydramine using flow injection (FI). The reagent selected was Bromophenol Blue. The chemical and FI variables were optimized. The calibration graph was linear over the concentration range 50-230 p.p.m. of diphenhydramine hydrochloride. A number of interfering substances were also investigated.
Diphenhydramine Spectrophotometry Turbidimetry Filtration Dilution Calibration pH Precipitation Optimization Interferences

"Continuous-flow Chemiluminescence Determination Of Isoniazid By Oxidation With N-bromosuccinimide"
Analyst 1990 Volume 115, Issue 9 Pages 1229-1234
Stergios A. Halvatzis, Meropi M. Timotheou-Potamia and Antony C. Calokerinos

Abstract: Powdered tablets equivalent to 200 mg of isoniazid (I) were dissolved in water, filtered and diluted with water to give a final solution containing 0.05 to 20 µg mL-1 of I and 1.0 M-NaOH and 0.5 mM NH3. I was reacted with 15 mM N-bromosuccinimide solution in a continuous-flow chemiluminescence analyzer. (illustrated), reagent and sample flow rates were 2.5 and 3.9 mL min-1, respectively. Detection was by photomultiplication. The limit of detection was 0.024 µg mL-1 and the coefficient of variation (n = 10) for 0.2 and 1.0 µg mL-1 were 3.0 and 0.9% respectively. Recoveries of 0.2 µg mL-1 in the presence of a tenfold concentration. of fifteen additives used as excipients were 97.5 to 103.9% and for 0.2, 0.4 and 0.8 µg mL-1, were 96.0 to 104.2%. The results were compared with those obtained by the BP official method and gave a mean relative difference of 2.4%.
Isoniazid Chemiluminescence Filter Dilution Detection limit Standard method

"Continuous-flow Chemiluminescence Determination Of Some Corticosteroids"
Analyst 1990 Volume 115, Issue 12 Pages 1553-1557
Ioanna I. Koukli and Antony C. Calokerinos

Abstract: Powdered tablets (200 mg), injection solution (2 ml) or creams (1 g) were dissolved in and diluted with 0.1 M H2SO4 for dexamethasone (I) and hydrocortisone (II) or 0.1 M H2SO4 containing 1% acetone for prednisolone (III), methylprednisolone (IV), dexamethasone (V) or betamethasone (VI). Portions of solution were analyzed in an air-segmented continuous-flow manifold by mixing the sample stream (2 mL min-1) with 0.5 mM ammonium Ce(IV) sulfate in 0.1 M H2SO4 and with aqueous 0.01 M Na2SO3 (both at 0.8 mL min-1) and the resulting chemiluminescence was measured. Calibration graphs were rectilinear from 0.1 to 1 µg mL-1 of I, II, III and IV, and from 0.5 to 5 µg mL-1 of V and VI with detection limits of 0.02 to 0.3 µg mL-1. The coefficient of variation were 1.3 to 4.9% and 1.6 to 6.2% for I and II, respectively. There was no interference from excipients. The sampling rate was 40 h-1. Results agreed well with those of an official method.
Corticosteroids Chemiluminescence Dilution Segmented flow Calibration Detection limit Method comparison Interferences Standard method

"Flow Injection Stopped-flow Kinetic Determination Of The Anxiolytic Sedative Bromazepam In Dosage Forms"
Analyst 1992 Volume 117, Issue 4 Pages 773-776
Salah M. Sultan

Abstract: Bromazepam was chelated with 0.072 M Fe(II) in 0.02 M HCl at 3.81 mL min-1 and was measured at 585 nm. The calibration graph was rectilinear from 1.8 to 5.6 mM with a coefficient of variation of 0.66% (n = 5) and a recovery of 99.9%. A highly selective and accurate flow injection (FI) method for the determination of bromazepam is based on the chelation of bromazepam with iron(II) to form a complex that absorbs at a max. wavelength of 585 nm. Optimization of FI and chemical parameters was achieved by the univariate and the computerized modified simplex methods. The drug (157 µL) is injected into 0.072 mol L-1 iron(II) solution, both previously prepared in 0.02 mol L-1 HCl, at a flow rate of 3.81 mL min-1 and allowed to mix and react in a coil for a fixed time of 300 s. A relative standard deviation of 0.66% with a recovery of 99.9% is achieved and the method is suitable for the determination of bromazepam in tablets.
Bromazepam Spectrophotometry Complexation Simplex Optimization Selectivity Kinetic Stopped-flow

"Flow Injection Spectrophotometric Determination Of The Antibiotic Ciprofloxacin In Drug Formulations"
Analyst 1992 Volume 117, Issue 9 Pages 1523-1526
Salah M. Sultan and Fakhr-Eldin O. Suliman

Abstract: A flow injection spectrophotometric method for the assay of ciprofloxacin was developed. The method was based on the chelation of iron(III) with the drug in 0.023 mol L-1 sulfuric acid solution in a 72 cm long coil and the brown-red complex produced was monitored at 447 nm. The super modified simplex computer program was employed for the optimization of the system and chemical parameters with respect to throughput and sensitivity as a measure of system performance. A working range for ciprofloxacin determination of 50-500 ppm for a 110 mm3 sample size with an optimum of 250 samples per hour was achieved with a relative standard deviation of less than 0.92%. The method was successfully applied to the determination of ciprofloxacin in drug formulations. Drug sample (110 µL) was injected into the carrier stream (5.8 mL min-1) of 31.8 mM Fe(III) in 23 mM H2SO4. The reactants were passed through a reaction coil (72 cm x 0.5 mm) and the absorbance of the brown - red complex was measured at 447 nm. The super modified simplex computer program was employed to optimize the system and chemical parameters with respect to throughput and sensitivity. Calibration graphs were rectilinear from 50 to 500 ppm. Sampling frequency was 250 h-1; coefficient of variation was 0.9% (n = 6). The method was applied to CiproBay tablets and infusion; recoveries were quantitative. A flow injection spectrophotometric method for the assay of ciprofloxacin (I) in bulk and formulations was based on the chelation of Fe(III) with the drug in 0.023 mol L-1 H2SO4 solution in a 72-cm long coil and the brown-red complex produced was monitored at 447 nm. The super modified simplex computer program was employed for the optimization of the system and chemical parameters with respect to throughput and sensitivity as a measure of system performance. A working range for I determination of 50-500 ppm for a 110 mm3 sample size with an optimum of 250 samples/h was achieved with a relative standard deviation of <0.92%.
Ciprofloxacin Spectrophotometry Simplex Optimization

"Chemometric Optimization And Flow Injection Method For The Determination Of Norfloxacin In Drug Formulations"
Analyst 1993 Volume 118, Issue 5 Pages 573-576
Salah M. Sultan and Fakhr Eldin O. Suliman

Abstract: For the cited method for the determination of norfloxacin (I), a factorial design program was utilized to establish the highly interacting factors to be optimized, and the optimization was performed by use of the super modified simplex method. In the optimized method, sample solution was injected into 0.0271 M Fe(III) in a 0.043 M H2SO4 carrier stream (5.33 mL min-1) and the was mixture passed through a PTFE reaction coil (45 cm x 0.5 mm) before the absorbance of the colored complex formed was monitored at 430 nm. The single-line flow injection manifold used is shown schematically. The calibration graph was rectilinear from 50 to 450 ppm of I and a sample throughput of 140 h-1 could be achieved. With use of the cited method, I was successfully determined in tablets after dissolution in warm water, acidification with dilute H2SO4 and filtration. The recovery was 100.7% and the coefficient of variation was 0.55%.
Norfloxacin Spectrophotometry Optimization Chemometrics Simplex Factorial design

"Determination Of Ascorbic Acid By Flow Injection With Chemiluminescence Detection"
Analyst 1993 Volume 118, Issue 6 Pages 639-642
Abdulrahman A. Alwarthan

Abstract: Flow injection and chemiluminescence detection were used to determine 30 amol of ascorbic acid based on the reducing effect of ascorbic acid on Fe(III) and measuring the Fe(II)-catalyzed light emission from luminol oxidation by H2O2. The method was used to determine ascorbic acid levels in tablets, capsules, syrup and fruit juices. The flow cell was a coil made of 1.3 mm i.d. glass tubing spiralled to a diameter of 35-mm. The photomultiplier tube was operated at 400 V. The acidified Fe(III) solution was used as the carrier stream for the sample which was acidified with 1% metaphosphoric acid. The luminol was mixed with the carrier solution at the reaction coil. Each solution was pumped (2.03 mL min-1) by a peristaltic pump. The calibration plot was rectilinear from 10 pM to 100 nM ascorbic acid. The detection limit was 30 amol. The coefficient of variation (n = 10) was 1.4% (for an injection of 1 µM). Recoveries ranged from 90.8 to 101.1% and 95.5 to 106.4% for pharmaceutical preparations and fruit juices, respectively.
Ascorbic acid Chemiluminescence

"Photochemical Spectrophotometric Determination Of Riboflavine And Riboflavine 5'-phosphate By Manual And Flow Injection Methods"
Analyst 1994 Volume 119, Issue 6 Pages 1199-1203
Tom&aacute;s Perez-Ruiz, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Otilia Val

Abstract: For the manual analysis, 0.2 M phosphate buffer of pH 7.2 was mixed with 3% Triton X-100, 1 mM MnSO4 and 16 mM dianisidine. Sample solution was added to the mixture before dilution with water. The solution was irradiated at 25°C and the absorbance at 460 nm was recorded as a function of the irradiation time. Calibration graphs were linear from 0.1-5 µM-riboflavine (I) and -riboflavine 5'-phosphate (II) with an RSD of 0.68%. For FIA, three reagent streams, viz, 2 mM dianisidine containing 0.45% Triton X-100 (0.7 ml/min), 0.1 M phosphate buffer of pH 7.2 (0.7 ml/min) and 0.1 mM MnSO4 (0.7 ml/min), were mixed. Sample solution was injected into the mixed reagent stream (2.1 ml/min) and transported to a reaction coil (100 cm x 0.5 mm i.d). The flow was stopped, the solution irradiated for 60 s and the absorbance at 460 nm was measured. A diagram of the manifold used is given. Calibration graphs were linear from 1-10 µM-I and -II; corresponding RSD were 1.3 and 1.1%. The throughput was 40 samples/h. Recoveries were quantitative for both methods. The methods were applied to multivitamin preparations and fortified bread.
Spectrophotometry Buffer Triton X Surfactant Photochemistry Stopped-flow

"Electrogenerated Chemiluminescent Determination Of Codeine And Related Alkaloids And Pharmaceuticals With Tris(2,2'-bipyridine)ruthenium(II)"
Analyst 1995 Volume 120, Issue 10 Pages 2549-2552
Gillian M. Greenway, Andrew W. Knight and Paul J. Knight

Abstract: A flow injection method for the determination of codeine (I), heroin (diamorphine; II) and dextromethorphan (III), based on electrogenerated chemiluminescence (CL), is described. The sample was pre-mixed with 1 mM tris(2,2'-bipyridine)ruthenium(II) and a portion (100 µL) of the resulting solution was injected into a carrier stream (2 ml/min) of either 0.05 M acetate buffer of pH 4 for I, 0.05 M acetate buffer of pH 5.5 for II or 0.05 M phosphate buffer of pH 6.5 for III. The mixture was carried to a flow cell containing the working electrode held at +1.39, +1.3 and +1.25 V, respectively, vs. a Ag-metal pseudo-reference electrode for I, II and III and the CL intensity produced was measured. Calibration graphs were linear from 0.1-10 µM of each drug and the detection limits were 15, 45 and 44 nM, respectively, of I, II and III. Results compared well with those obtained by GC-MS and other CL methods. The RSD (n = 5) were 5%. The method was applied to the determination of I in C0-codaprin tablets, with a recovery of 103.8%. This work describes a novel and sensitive method for the determination of codeine, heroin, and dextromethorphan, using flow injection with electrogenerated chemiluminescence (ECL). The method is based on the ECL reaction of tris(2,2'-bipyridine) ruthenium(II) with tertiary amino groups. The factors affecting the determinations were investigated and possible reaction inhibitors, such as phenolic functional groups, were identified. Linear calibrations were obtained for signal (mV) versus concentration (µmol l-1) in the range 0.1-1.0 µmol L-1 with percentage relative standard deviations of less than 5% (n = 5). The 50 limits of detection were calculated as 15, 45 and 44 nmol L-1 for codeine, heroin, and dextromethorphan, respectively. (11 References)
Codeine Dextromethorphan Drugs Heroin Chemiluminescence Electrode Method comparison

"Use Of A Sequential Injection Technique For Mechanistic Studies And Kinetic Determination Of Bromazepam Complexed With Iron(II) In Hydrochloric Acid"
Analyst 1996 Volume 121, Issue 5 Pages 617-621
Salah M. Sultan and Fakhr Eldin O. Suliman

Abstract: A kinetic investigation of the complexation reaction of bromazepam (I) with Fe(II) in HCl was carried out using a sequential injection technique. A reaction mechanism is proposed. In addition, the following method for I determination was developed. Fixed volumes of Fe(II) and HCl solutions were aspirated into a holding coil and then pushed into a mixing chamber together with aqueous carrier solution. The final Fe(II) and HCl concentrations in the mixing chamber were 0.01 and 0.0115M, respectively. A known volume of the sample was then withdrawn into the holding coil and subsequently also pushed into the mixing chamber together with aqueous carrier solution. After 100 s, a known volume of solution was withdrawn from the mixing chamber and transferred into the holding coil before being pushed to a spectrophotometric detector where the absorbance was measured at 585 nm. A diagram of the manifold used is given. The calibration graph was linear for 0.5-1.5 mM I. The method was applied to pharmaceuticals (tablets), giving an RSD (n = 6) of 1.2% and quantitative recovery of I.
Bromazepam Spectrophotometry Sequential injection Kinetic

"Cyclodextrin-based Optosensor For The Determination Of Riboflavin In Pharmaceutical Preparations"
Analyst 1996 Volume 121, Issue 8 Pages 1119-1122
Zhilong Gong and Zhujun Zhang

Abstract: Tablets were dissolved in H2O; a portion was mixed with 5 mL 0.1 M NaH2PO4/0.1 M Na2HPO4 buffer of pH 6.5 (buffer A) and the mixture was diluted to 25 mL with water. A portion (2 ml) of the resulting solution was injected into a carrier stream of buffer A at a flow rate of 2 ml/min and passed through a 25 µL flow-through cell containing β-cyclodextrin immobilized on to silica gel. The fluorescence intensity of the adsorbed riboflavin/β-cyclodextrin complex was measured at 521 nm (excitation at 468 nm). The calibration graph was linear from 0.2-20 µM-riboflavin; the detection limit was 9 ng/ml. RSD was 1% (n = 7) at the 0.05 µg/ml riboflavin level.
Riboflavine Fluorescence Sensor Silica gel Immobilized reagent

"Sensitive Determination Of Digoxin In Tablets By Flow Injection With Fluorescence Detection"
Analyst 1996 Volume 121, Issue 11 Pages 1613-1616
M. S. Bloomfield, S. Matchett and K. A. Prebble

Abstract: Tablets were extracted ultrasonically with aqueous 96% ethanol for bulk or single tablet assays and with water for dissolution testing. The extracts were filtered and portions (25 µL) of the filtrate were injected into a reagent stream (1 ml/min) of ethanolic HCl containing ascorbic acid and benzoyl peroxide in a flow injection manifold (schematic shown). The mixture was passed through a 100 cm coil maintained at 75°C and the fluorescence intensity was measured at 488 nm (excitation at 364 nm). The calibration graph was linear up to 15 and 3.75 µg/ml, respectively, for digoxin in aqueous 96% ethanol and water. The RSD (n = 10) were Recoveries of digoxin added to tablets were quantitative.
Digoxin Fluorescence

"Clean Method For The Simultaneous Determination Of Propyphenazone And Caffeine In Pharmaceuticals By Flow Injection Fourier Transform Infrared Spectrometry"
Analyst 1997 Volume 122, Issue 5 Pages 441-445
Zouhair Bouhsain, Salvador Garrigues and Miguel de la Guardia

Abstract: Powdered tablets (100-150 mg) were dissolved in 7 mL CHCl3. The solution was filtered and the filtrate was made up to 10 mL. For flow injection (FI) measurements, a portion (300 µL) was injected into a carrier stream of CHCl3 at a flow rate of 1.23 ml/min. A FTIR spectrum was recorded, accumulating 2 scans. Stopped-flow measurements were also made on the CHCl3 solution of the sample, 16 scans being accumulated. In both cases, a 0.5 mm bandpass and a nominal resolution of 4 cm-1 were employed. Propyphenazone (I) was determined by measuring the peak-height absorbance at 1595 cm-1, corrected with a baseline established from 2000-890 cm-1. Caffeine (II) was determined by measuring the first-derivative peak height at 1712 cm-1. Detection limits were 0.03 mg/ml I and 1.5 mg/ml II for the FI mode; RSD were 1-2.1% (n = 5). Detection limits were 0.06 mg/ml I and 0.45 mg/ml II for the stopped-flow mode; RSD was 0.5% (n = 5). A distillation unit was incorporated into the FI manifold for online recycling of the CHCl3 used as carrier and solvent, thus avoiding the generation and accumulation of toxic waste. A procedure is proposed for the simultaneous FTIR determination of propyphenazone (PFZ) and caffeine (CAF) in pharmaceuticals. The method involves the dissolution of the active principles in CHCl3, followed by filtration of sample solutions to remove the excipients. PFZ is then determined by absorbance measurements at 1595 cm-1, using a baseline established between 2000 and 890 cm-1, and CAF by using the first-derivative values at 1712 cm-1, using solutions of PFZ and CAF for external calibration. The method was applied in both the stopped-flow and flow injection modes, providing precise and accurate results for the analysis of real samples. The incorporation of a distillation unit for the on-line recycling of the CHCl3 used as carrier and solvent provides an environmentally friendly analytical methodology which makes possible an injection frequency of 120 samples h-1 and reduces the cost and side-effects of the production of laboratory waste.
Caffeine Propyphenazone Spectrophotometry Spectroscopy Organic phase detection Organic solvent Stopped-flow Simultaneous analysis

"Flow Injection Spectrophotometric Determination Of Acetylsalicylic Acid In Tablets After Online Microwave-assisted Alkaline Hydrolysis"
Analyst 1998 Volume 123, Issue 5 Pages 1011-1015
Airton Vicente Pereira, Clezio Aniceto and Orlando Fatibello-Filho

Abstract: The proposed method is based on an online microwave-assisted alkaline hydrolysis of acetylsalicylic acid (ASA) to salicylic acid (SA) that reacts with Fe3+ to form a complex that absorbs light at 525 nm. Samples merged with NaOH were passed continuously through a domestic microwave oven in order to accelerate the hydrolysis of ASA. Under the best anal. conditions, the linearity of the calibration equation ranged from 25 to 250 µg ASA/mL. The precision for 10 successive measurements of 200 µg ASA/mL presented a relative standard deviation of 0.40%. The detection limit was 4.0 µg/mL and recoveries of 99.1-101.0% were obtained for ASA. No interference was observed from the common tablet excipients and other active substances such as ascorbic acid and caffeine. The proposed flow injection method is fast and permits the determination of ASA in 90 samples per h.
Acetylsalicylic acid Spectrophotometry Microwave Heated reaction Hydrolysis reaction Interferences

"Indirect Flame Atomic Absorption-spectrometric Determination Of Papaverine, Strychnine And Cocaine By Continuous Precipitation With Dragendorff Reagent"
J. Anal. At. Spectrom. 1993 Volume 8, Issue 8 Pages 1117-1120
Marcelina Eisman, Mercedes Gallego and Miguel Valc&aacute;rcel

Abstract: Samples of injection solution, oral drops or syrup were dissolved in H2O; ground tablets were extracted with water and the extract was filtered. The FIA system comprised blank and sample streams, into either of which Dragendorff reagent (0.8 mM tetraiodobismuthate of pH 2.0) was injected. The pH of the sample stream was 5.1-7.2 for papaverine (I), 3.5-7.5 for strychnine (II) or 3.0 for cocaine (III). The resulting stream was passed through a 200 cm mixing coil and filter and analyzed for Bi by flame AAS. The difference in absorbance between the sample and blank (H2O for I or II, 1 mM HCl for III) streams was related linearly to the concentrations of I, II and III over the ranges 1.5-18, 4-60 and 6-100 µg/ml with detection limits of 0.8, 1.5 and 2.5 µg/ml, respectively. The effects of pH, flow rate and temperature were investigated. The tolerance limits towards other common alkaloids are reported.
Papaverine Strychnine Cocaine Spectrophotometry Indirect Precipitation Interferences Filter

"Incorporation Of Electrodialyzers Into The Conduits Of Flow Injection-atomic Absorption Spectrometry Systems. Determination Of Copper(II) Ions In Multivitamin Tablets After Enhancement Of Mass Transfer Through A Passive Neutral Membrane"
J. Anal. At. Spectrom. 1998 Volume 13, Issue 1 Pages 23-28
Jacobus (koos) F. van Staden and Cornelius J. Hattingh

Abstract: An electrodialyzer unit was designed, incorporated into the conduits of a flow injection (FI) system and employed for the removal of suspended solids before detection by AAS. The combined electrodialyzer-FI-AAS system was applied to the determination of Cu(II) in multivitamin and mineral tablets. The proposed system is fully computerized and is able to determine Cu(II) in samples at a frequency of 14 samples h-1 with a sample interaction of 0.058. The electrodialysis efficiency was 94, which is a dramatic improvement over previous systems with passive neutral membranes. The calibration graph is linear between 1 and 60 mg l-1. The detection limit is 1.44 mg l-1. The results obtained for Cu(II) in multivitamin and mineral tablets with the proposed system compared favorably with those obtained with the standard manual AAS method.
Copper(II) Spectrophotometry Dialysis Membrane Automation Method comparison

"Continuous Determination Of Ascorbic Acid By Photobleaching Of Methylene Blue"
Anal. Chem. 1972 Volume 44, Issue 7 Pages 1267-1269
Vance R. White and J. M. Fitzgerald

Abstract: An apparatus for the determination of ascorbic acid, via the photobleaching of the methylene blue carrier stream, was discussed and the appropriate diagram presented. The signal was measured by an Atomic Absorption (AA) spectrophotometer and a major advantage to the system is its ability to regenerate the methylene blue carrier stream via the oxidation of methylene blue by diatomic oxygen. Day to day reproducibility was very good and a discussion of interferences (mostly from aromatic components) is presented along with a table outlining the various interference levels. A discussion of the results for the analysis of orange juice, water, and vitamin C tablets are presented.
Ascorbic acid Spectrophotometry Apparatus Indirect Interferences Photochemistry

"Characterization Of Solvent Extraction/flow Injection Analysis With Constant Pressure Pumping And Determination Of Procyclidine Hydrochloride In Tablets"
Anal. Chem. 1982 Volume 54, Issue 11 Pages 1693-1697
Lynette Fossey and Frederick F. Cantwell

Abstract: A flow injection extraction apparatus utilizing a membrane phase separator and constant pressure pumping is described and characterized In terms of extraction coil length, sample injection volume, and flow rates. Equations are derived and verified that show that under conditions where the sample component is quantitatively extracted into the organic phase, the peak area depends only on the number of moles of sample injected and the total flow rate of organic solvent. A sampling frequency of 4 samples/min is readily achieved. Procyclldlne hydrochloride is assayed in tablets with 1% precision and accuracy.
Procyclidine HPLC Sample preparation Phase separator Constant pump pressure Review Solvent extraction Membrane

"Simultaneous Monitoring Of Both Phases In The Solvent Extraction/flow Injection Analysis Of Dramamine Tablets"
Anal. Chem. 1983 Volume 55, Issue 12 Pages 1882-1885
Lynette Fossey and Frederick F. Cantwell

Abstract: The extraction - flow injection system described and illustrated is equipped with a dual-membrane phase separator having a PTFE membrane that permits passage of organic phase and a hydrophilic membrane (Whatman No. 5 paper) that permits passage only of aqueous phase.A solution (44 µL) of the finely ground tablets [containing diphenhydramine(I) and 8-chlorotheophylline(II)] in phosphate buffer solution (pH 7) is injected into a flowing carrier solution (aqueous NH3 - NH4Cl to give aqueous 0.66 M NH3 at pH 10.2) into which a stream of cyclohexane flows.In an extraction coil, I is quantitatively extracted into the cyclohexane; II remains in the aqueous phase. The phases are separated, and the absorbance is measured at 254 nm (for I in the organic phase) and 300 nm (for II in the aqueous phase). Calibration graphs (based on peak areas) are prepared with 0.25 to 2 mM I in cyclohexane and with 0.25 to 2.5 mM II in aqueous solution Precision and accuracy are excellent. One analysis takes ~0.5 min.
8-Chlorotheophylline Diphenhydramine Spectrophotometry Sample preparation Phase separator Teflon membrane Hydrophilic membrane Hydrophobic membrane Simultaneous analysis Organic phase detection Solvent extraction

"Subtractive Anodic Stripping Voltammetry With Flow Injection Analysis"
Anal. Chem. 1984 Volume 56, Issue 2 Pages 156-159
Joseph Wang and Howard D. Dewald

Abstract: In this approach to subtractive anodic-stripping voltammetry, the analytical and background voltammograms are recorded while the sample and carrier solution, respectively, flow-through the detector; the carrier contribution is then subtracted. Effective correction for faradaic and non-faradaic background current contributions afforded a detection limit for Cd of ~0.14 ng (6 nM) with a 1-min deposition time. Non-deaerated samples could be used, owing to effective correction of the O reduction current. Simultaneous measurement of several trace metals at the ppb level by using 200 µL samples is possible and an injection rate of up to 24 samples h-1 can be achieved. Applications to multivitamin plus minerals tablets are described.
Cadmium Copper Lead Zinc Voltammetry PPB Simultaneous analysis

"Flow Injection Determination Of Penicillins Using Immobilized Penicillinase In A Single Bead String Reactor"
Anal. Chem. 1985 Volume 57, Issue 6 Pages 1005-1009
R. Gnanasekaran and Horacio A. Mottola

Abstract: Procedures for etching the glass beads with NH4HF2, silylation with (aminophenyl)trimethoxysilane, activation with glutaraldehyde and immobilization of penicillinase on the glass beads are described in detail. With use of optimum reaction conditions established for the flow injection determination of penicillins (at pH 6.4, 25°C and a flow rate of 4 mL min-1), benzylpenicillin was determined in tablets and injection solution and phenoxymethylpenicillin was determined in fermentation broths. Rectilinear calibration graphs were obtained for concentration. up to 5 mM of each drug.
Benzylpenicillin Phenoxymethylpenicillin Penicillins Potentiometry Glass beads Immobilized enzyme Optimization Single bead string reactor

"Theoretical And Experimental Response Of A Biamperometric Detector For Flow Injection Analysis"
Anal. Chem. 1985 Volume 57, Issue 7 Pages 1377-1381
T. P. Tougas, J. M. Jannetti, and W. G. Collier

Abstract: The detector consists of two opposing platinum electrodes in contact with the carrier stream. A p.d. of 10 to 500 mV is applied between the electrodes and the resulting current is measured. The current can flow only when both reduced and oxidized forms of a couple are present in the cell. The method is demonstrated with the Fe(CN)63- - Fe(CN)64- couple, and was applied to the determination of Fe(II) in multivitamin preparations, the results agreeing closely with those obtained by the phenanthroline method.
Iron(2+) Amperometry Electrode Method comparison Theory

"Solvent Extraction-flow Injection Without Phase Separation Through The Use Of The Differential Flow Velocities Within The Segmented Flow"
Anal. Chem. 1994 Volume 66, Issue 14 Pages 2220-2225
Charles A. Lucy and Ken K.-C. Yeung

Abstract: A solvent extraction-flow injection manifold is described that does not require a phase separator or an on-tube detector and quantifies both extracted and unextracted components from a single injection. The sample was injected into an aqueous phase and a hexanol-water segmented flow was established in the extraction coil. The wetting film of the organic phase formed on the walls of the Teflon tubing reduced the linear velocity of the organic flow, and the differential flow velocities yielded a separation in time between the unextracted and extracted components. The segmented flow was merged with a methanol stream and entered a mixing coil for homogenization before passage through the flow cell of an absorbance detector for monitoring at 254 nm. Large aqueous-to-organic ratios, high flow rates and long extraction coils enhanced the resolution. The method was applied to the determination of the active components in motion sickness tablets, with a throughput of 12 samples/h and a precision of 2.5 and 4% for 8-chlorotheophylline and diphenhydramine, respectively.
8-Chlorotheophylline Diphenhydramine Spectrophotometry Sample preparation Phase separator Solvent extraction

"Spectrophotometric Determination Of Dopamine And Methyldopa With Metaperiodate By Flow Injection Analysis"
Fresenius J. Anal. Chem. 1995 Volume 353, Issue 2 Pages 221-223
J. J. Berzas Nevado Contact Information, J. M. Lemus Gallego and P. Buitrago Laguna

Abstract: Tablets were dissolved in 0.02 M acetate buffer of pH 4.8 to give a concentration of 8 M dopamine or methyldopa with ultrasonication followed by filtration. Aqueous formulations of dopamine and methyldopa were diluted with the above buffer to give a concentration of 20-200 µM. The resulting solutions were analyzed by FIA as previously described (Anal. Chim. Acta, 1995, 300, 293) with reactor set at 45°C for methyldopa and at 65°C for dopamine and detection at 473 nm. Calibration graphs were linear up to 20 mM catecholamines with a detection limit of 0.59 µM-dopamine and 0.32 µM-methyldopa; RSD (n = 10) were 0.402 and 0.463%, respectively.
Methyl dopa Dopamine Spectrophotometry Heated reaction

"Determination Of Total Iron In Groundwaters And Multivitamin Tablets Using A Solid Phase Reactor With Tiron Immobilized On Amberlite Ion-exchange Resin In A Flow Injection System"
Fresenius J. Anal. Chem. 1998 Volume 362, Issue 3 Pages 319-323
J. F. van Staden and L. G. Kluever

Abstract: A method is described for the flow injection determination of total Fe as Fe(III) (Fe(II) was oxidized before determination) using a solid phase reactor containing disodium-1,2-dihydroxybenzene-3,5-disulfonate (tiron) as substrate. The Fe(III) reacted with tiron and formed a complex which absorbed at 667 nm, where it was measured spectrophotometrically. The system has a linear range of 1-50 mg L-1 with a detection limit of 0.67 mg L-1. The method was applied to the determination of total Fe in multivitamin tablets and iron-rich ground waters, with a RSD <1.1%. The results agreed with certified values and results of a standard ICP-AES method.
Iron Spectrophotometry Solid phase reagent Tiron Amberlite Complexation Method comparison Reference material

"Flow Injection Analysis Of Warfarin Sodium With Amperometric Detection"
Microchim. Acta 1985 Volume 86, Issue 3-4 Pages 145-151
Fathalla Belal and James L. Anderson

Abstract: Dosage forms containing 1 to 40 µg mL-1 of warfarin sodium were injected into a stream (1 mL min-1) of methanol - aqueous phosphate - acetate buffer solution of pH 7 (1:1) and the current was measured at a vitreous-carbon electrode at +1.05 V vs. the silver - AgCl electrode. The calibration graph was rectilinear from 1 to 40 µg mL-1 and the limit of detection (signal-to-noise ratio of 2:1) was 5 ng mL-1. At concentration. of 10, 20, 30 and 40 µg mL-1, the coefficient of variation (n = 4) were 0.4, 0.2, 0.4 and 0.2%. The proposed method gave results in good agreement with those obtained with the USP 1980 method when applied to Coumadin tablets and injections. Up to 200 samples can be analyzed in 1 h.
Warfarin sodium Amperometry Clinical analysis Electrode

"Indirect Flow Injection Determination Of Ascorbic Acid By Flame Atomic Absorption Spectrometry"
Microchim. Acta 1997 Volume 126, Issue 1-2 Pages 53-58
M del Carmen Yebra-Biurrun, Rosa Maria Cesp&oacute;n-Romero and Pilar Bermejo-Barrera

Abstract: A portion (85 µL) of 75 µg/ml Fe(III) in 0.5 M HNO3 was injected into a flow (0.6 ml/min) of 2.5 mM 1,10-phenanthroline, which merged with a flow (2.3 ml/min) of aqueous sample solution containing ascorbic acid (diluted fruit juice, dissolved sweets or dissolved tablets), passed through a PTFE mixing coil (100 cm x 0.8 mm i.d.), merged with a flow (1.6 ml/min) of 9 mM picric acid, passed through a PTFE reaction coil (100 cm x 0.8 mm i.d.) and then through a 0.1 g Amberlite XAD-4 resin column (0.95 cm x 1.6 mm i.d.) prior to AAS detection at 248.3 nm. The signal response was caused by Fe(III), and increased with decreasing ascorbic acid concentration. The calibration graph was linear from 0.5-25 µg/ml ascorbic acid, the detection limit was 0.2 µg/ml and the RSD (n = 11) at 10 µg/ml was 2.9%. Recoveries were 96.1-103.7% and the sample throughput was 90/h. Up to 50-fold excesses of potential interferents did not affect the results (details given).
Ascorbic acid Spectrophotometry Reverse Indirect Interferences Amberlite

"Plastic Membrane Electrodes For The Potentiometric Determination Of Codeine In Pharmaceutical Preparations"
Microchim. Acta 1997 Volume 126, Issue 1-2 Pages 147-151
Eman M. Elnemma and M. A. Hamada

Abstract: The precipitates resulting from the mixing of codeine phosphate and tetraphenylborate or ammonium reineckate solutions were dried and ground. Portions were dissolved in THF, along with PVC powder and plasticizer (dioctyl phthalate or dibutyl sebacate), and the mixtures were evaporated in petri dishes, giving codeine-PVC membranes which were used to fabricate ISE. Crushed tablets were dissolved in aqueous citrate/phosphate buffer solution and potentiometrically analyzed using a codeine-PVC membrane electrode with a Ag/AgCl reference electrode. Pharmaceutical syrup was diluted with the same buffer and similarly analyzed. The electrode was also used for the potentiometric titration of codeine (I) solutions against sodium tetraphenylborate. The applicability of the electrode to FIA was investigated by determinations of I in samples injected into a flow of buffer and potentiometric detection using a sandwich cell incorporating the electrode. For the bulk methods, the calibration graphs were linear from 0.1-10 mM I and detection limits were 0.03-0.07 mM I. The electrodes were stable from pH 3-7. Recoveries from pharmaceuticals averaged 100.6%, and RSD (n = 3) averaged 0.8%. Titrimetric and FIA methods performed similarly, and the FIA method enabled the detection of down to 1 µM-I.
Codeine Potentiometry Electrode Buffer Method comparison Sensitivity

"Rapid Determinations Of Some 1,4-benzodiazepines By Flow Injection Analysis"
Microchem. J. 1988 Volume 37, Issue 3 Pages 257-262
D. Prada, E. Lorenzo, M. Hern&aacute;ndez and L. Hern&aacute;ndez*

Abstract: The inherent absorption properties of bromazepam, chlordiazepoxide and lorazepam were used in their determination in formulations and in urine, with a sampling rate capability of 120 h-1. Tablets were dissolved in methanol and the supernatant solution was diluted with 9 volume of 0.1 M acetate buffer (pH 4.5). Urine samples were buffered to pH 7.0 with phosphate solution and the drugs were extracted into ethyl ether. The ether solution was evaporated to dryness and the residue was dissolved in acetate buffer (pH 4.5) - methanol (9:1). Absorption max. were at 233 nm (bromazepam and lorazepam) and 244 nm (chlordiazepoxide). For determinations of 1.2 to 2.4 µg mL-1 of drug (n = 10), coefficient of variation were 2.0%.
Bromazepam Chlordiazepoxide Drugs Lorazepam Spectrophotometry Optimization

"Fluorimetric Determination Of Captopril By Flow Injection Analysis"
Microchem. J. 1991 Volume 43, Issue 3 Pages 176-180
R. Segarra Guerrero, S. Sagrado Vives, J. Martinez Calatayud

Abstract: Sample solution (140 µL) was directly injected into the carrier - reagent stream (2.0 mL min-1), which consisted of a solution of Ce(IV) ions (100 ppm) in 0.25 M H2SO4. The Ce(III) formed by the oxidation reaction in the coil (length 280 cm) was monitored fluorimetrically (excitation and emission at 259 and 359 nm, respectively). The calibration graph was rectilinear for 1.0 to 5.0 ppm, the coefficient of variation at 2.0 ppm was 1.3%, and the analysis rate was 145 samples hr-1. Most compounds used as excipients in pharmaceutical samples did not interfere; however compounds having reductive properties (e.g., ascorbic acid or NaSO3) interfered even at low levels. The method was used to determine captopril in Capoten and Tensoprel tablets.
Captopril Fluorescence Interferences

"Determination Of Promethazine Hydrochloride With Bromophenol Blue By A Turbidimetric Method And Flow Injection Analysis"
Microchem. J. 1992 Volume 45, Issue 2 Pages 129-136
J. Martinez Calatayud*, a,*, S. Navasquillo Sarriona, A. Sanchez Sampedrob and C. Gomez Benitob

Abstract: The drug was extracted from the tablets with water and a portion (91.8 µL) was injected into the carrier reagent stream (0.97 mL min-1) which consisted of a mixture of 1.16 mM bromophenol blue and 86 mM KCl which was adjusted to pH 1.20 with HCl. The reaction coils were Teflon tubes (0.5 mm i.d.) and the turbidity was measured in an 18 µL flow cell at 650 nm. The calibration graph (peak height) was rectilinear from 25 to 197 ppm of promethazine with a coefficient of variation (n = 30) of 1.3%; the sample injection rate was 32 h-1. The tolerance of this method to some foreign compounds is also reported. A flow injection analysis procedure for the turbidimetric determination of promethazine is proposed. The sample solution is injected directly into the carrier reagent stream, which is composed of 1.16 x 10^-3 M bromophenol blue at pH 1.20. The calibration graph is linear over the range 25-197 ppm of promethazine. The influence of some foreign substance was also investigated. The method was applied to promethazine determination in a pharmaceutical formulation.
Promethazine hydrochloride Turbidimetry Interferences pH

"Study On Cobalt-PTFE Composite-plated Electrode And Its Electrochemical Properties"
Microchem. J. 1996 Volume 53, Issue 4 Pages 385-394
Hongding Xu, Mingzhu Zou, Qinhua Ru and Yunjing Luo

Abstract: A Ni disc electrode and a Co plate (0.196 cm2) were placed in an electroplating bath of pH 4-4.2 and 62±1°C. For the Co layer deposition, the bath contained 10.8 g CuSO4/NaCl/boric acid (10:1:1) in 40 mL water at 40 mA/cm2 and 9°C. For the Co-PTFE layer, the bath was 9.525 g CuSO4/NaCl/boric acid (3:10:1) in 30 mL water at 30 mA/cm2 and 1.5 C. The electroplating was carried out using a PAR173/179 potentiostat-coulometer. The resulting electrode surface was characterized by XPS and scanning electron microscopy. The chronoamperometric responses of this electrode to alcohols were studied. The electrode was also used in an FIA system with Ag and Pt wire reference and auxiliary electrodes, respectively. The responses to vitamins, amino-acids and monosaccharides were studied. The method was also applied to drug tablet analysis. The surfaces of the composite-plated electrode were smooth and uniform with PTFE particles embedded in the plated layer. The linear calibration graphs for fatty alcohols are given; detection limits were 1-10 mM. Calibration graphs were linear for the several biochemical compounds tested (ranges given); detection limits were from 1 µM-0.1 mM; RSD were 0.12-1.78%. Recoveries were from 95-105% vitamin B2 (riboflavine) in tablets.
Riboflavine Potentiometry Electrode Apparatus

"Determination Of Trace Elements In Pharmaceutical Tablets Using Anodic-stripping Voltammetry"
Anal. Lett. 1983 Volume 16, Issue 12 Pages 925-939
Joseph Wang; Howard D. Dewald

Abstract: A Bioanalytical System electrochemical cell (model VC-2) was used; it had a vitreous-carbon electrode, a platinum-wire auxiliary electrode and a silver - AgCl reference electrode, and a fresh mercury film was deposited on the carbon electrode each day.The sample solution was prepared by dissolving a multivitamin tablet, containing <3 mg of Cu or Zn, in 1 M HNO3 and diluting this solution to 100 ml.Electro-deposition was effected at -0.8 V from 0.1 M KNO3 or 1 M HNO3 as supporting electrolyte, and a potential scan at 0.5 V min-1 (differential pulse amplitude 50 mV) was then applied.A gravity-flow injection system (Rheodyne model 7010 with a 200 µL sample loop) with a wall-jet detector is described; an injection rate of 15 h-1 was attainable.The connecting PTFE tubing was 0.5 mm in diameter and the carrier flow rate was 0.4 mL min-1.Stripping voltammograms were recorded with a Sargent-Welch polarograph (model 4001).Mutual interference between Cu and Zn was avoided by the addition of an excess of Ga (to prevent co-deposition of Cu and Zn) or by use of a dual-working-electrode system (selective deposition at different potentials).
Voltammetry Electrode Interferences

"Aqueous Flow Injection Analysis With Fourier Transform Infrared Detection"
Anal. Lett. 1985 Volume 18, Issue 16 Pages 1979-1998
Morgan, D.K.;Danielson, N.D.;Katon, J.E.

Abstract: A Barnes cylindrical internal reflection cell containing a zinc selenide crystal (diameter 0.318 cm) as internal reflector mounted in a stainless-steel high-pressure flow cell (25 µL) was used to connect a flow injection system with automated sample injection to a Digilab FTS-14C/D spectrometer with a coiled hot-wire source and a TGS detector. When the apparatus was used to determine Na dioctyl sulfosuccinate(I) in aqueous solution at 1234 or 1728 cm-1, the detection limit was 0.77 mg and coefficient of variation were 2 to 7% (n = 5) under stopped-flow conditions and were lower than those obtained in the flowing mode. The analyis rate was 25 samples per hour. The assembly was also used to analyze tablets containing I, capsules containing the Ca salt of I and aqueous solution of methicillin sodium.
Dioctylsulfosuccinate Spectrophotometry Stopped-flow

"Determination Of Paracetamol By A Flow Injection Spectrophotometric Method"
Anal. Lett. 1986 Volume 19, Issue 19&20 Pages 2023-2038
Martinez Calatayud, J.;Pascual Marti, M.C.;Sagrado Vives, S.

Abstract: Tablets are dissolved with water, the solution is made 0.4 M in aqueous NH3 and paracetamol (I; 0.25 to 30 ppm) is determined by oxidation at 80°C with K3Fe(CN)6 to form N-acetyl-p-benzoquinonimine. The compound is then caused to react with phenol to form N-(4-hydroxyphenyl)-p-benzoquinonimine and the absorbance of the blue solution is measured at 630 nm. For 10 ppm of I, salicylic acid, phenobarbitone, citric acid, diazepam, phenylephrine, aspirin, caffeine, and aged ascorbic acid solution do not interfere at levels from 50 to 250 ppm. The proposed method was applied to the determination of I in various pharmaceuticals.
Drugs Acetaminophen Spectrophotometry Heated reaction Interferences

"Indirect Flow Injection Analysis Of Ascorbic Acid By Photochemical Reduction Of Methylene Blue"
Anal. Lett. 1993 Volume 26, Issue 8 Pages 1741-1750
Leon, L.E.;Catapano, J.

Abstract: Sample (185 µL) was injected into a carrier stream (1.5 ml/min) of buffered methylene blue solution of pH 3.2 (12.7 µg/ml). The stream was passed through a reactor coil (1.5 m x 0.7 mm) immersed in a thermostatically-controlled water bath at 32°C and irradiated by means of a 500-W halogen lamp. The resulting change in absorbance of the carrier solution was monitored at 666 nm. The detection limit was 0.34 µg/ml of ascorbic acid (I). The calibration graph was rectilinear for 0.18-6.12 µg/ml of I and RSD ranged from 0.3-2.1%. Glucose, fructose, saccharose, sodium tartrate, citric acid, sodium benzoate, maleic acid, caffeine and nicotine did not interfere. The cited method was applied in the analysis of vitamin C tablets. Results agreed well with those obtained by the official AOAC method.
Ascorbic acid Spectrophotometry Photochemistry Method comparison Standard method Interferences Indirect

"Flow Injection Analysis Of Famotidine With Spectrophotometric Detection"
Anal. Lett. 1993 Volume 26, Issue 10 Pages 2183-2191
Kamath, B.V.;Shivram, K.;Vangani, S.

Abstract: Powdered tablets equivalent to 40 mg of famotidine (I) were shaken with 60 mL of 0.2 M acetate buffer of pH 5 (buffer A) for 5 min. After dilution to 100 mL with buffer A, the mixture was filtered and a 100 µL portion of the filtrate was injected into a carrier stream of buffer A at 1.6 ml/min. This stream merged with a stream of 0.025 M cupric acetate at 0.8 ml/min then passed through a 2 m reaction coil before the absorbance was measured at 630 nm. A 5 mL portion of the initial filtrate was further diluted to 50 mL then subjected to analysis as above with the absorbance being monitored at 314 nm. Calibration graphs were linear for 10^-50 µg/ml of I with detection at 314 nm and 50-500 µg/ml with detection at 630 nm. Up to 60 samples an hour could be analyzed with a RSD of 1.4%. Recoveries were 98-100.6% and the results are comparable with those obtained by official methods.
Famotidine Sample preparation Spectrophotometry Method comparison

"Fluorimetric Determination Of Cisapride"
Anal. Lett. 1994 Volume 27, Issue 9 Pages 1713-1718
Gonzalez Martin, M.I.;Gonzalez Perez, C.;Blanco Lopez, M.A.

Abstract: Cisapride (I) was dissolved in methanol, diluted with water and analyzed spectrofluorimetrically at 355.2 nm (excitation at 310 nm). Calibration graphs were linear for 1-30 µM-I using a slit width of 5 nm with a detection limit of 32 nM using a slit width of 5 nm and for 1-400 µM-I with a detection limit of 65 nM using a slit width of 3 nm. At 20 mM I, a RSD of 1.3% was obtained. Using 8 mM Britton-Robinson buffer over the pH range 2-6 the fluorimetric response was constant and samples were stable for at least 50 min. A FIA system was also used with an optimum injection volume of 110 mL and a carrier (not specified) flow rate of 0.92 ml/min. With a slit width of 5 nm, peak height calibration graphs were linear over the range 8-400 µM-I with a detection limit of 6.5 µM. At 20 mM I a RSD of 2.2% was obtained. Both discontinuous and FIA analyzes were applied to the determination of I in tablets.
Cisapride Fluorescence

"FIA Fluorimetric Determination Of Calcium Pantothenate. Validation And Quantitation In Multivitamin Preparations"
Anal. Lett. 1995 Volume 28, Issue 5 Pages 821-833
Blanco, M.;Coello, J.;Iturriaga, H.;Maspoch, S.;Pages, J.

Abstract: Powdered tablets were suspended in 0.02 M HCl, sonicated for 10 min and centrifuged. The resulting solution was appropriately diluted and injected (35 µL) into the flow injection manifold (diagram given). Calcium pantothenate (I) was hydrolyzed in a 10 m loop by mixing with 0.6 M NaOH (0.9 ml/min) and heating at 85°C. Following hydrolysis, the solution was mixed with the derivatization solution (1 ml/min) comprising 0.373 mM o-phthaldialdehyde 38 µM-2-mercaptoethanol and 0.4 M H3BO3 in a 3 m coil. The emitted fluorescence was measured at 455 nm (excitation at 350 nm). The calibration graph was linear from 0.2-40 mg/l of I. The sampling rate was 25 samples/h. Detection and quantitation limits were 0.02 and 0.09 mg/l, respectively. The method was applied to multivitamin preparations.
Pantothenate Fluorescence Heated reaction

"Flow Injection Analysis Determination Of Ascorbic Acid With Spectrofluorometric Detection"
Anal. Lett. 1998 Volume 31, Issue 2 Pages 333-342
Ali A. Ensafi; B. Rezaei

Abstract: A flow injection system for the fluorescence determination of low level of ascorbic acid is proposed. The method is based on the rapid oxidation of ascorbic acid by Tl(I). The fluorescence signal at 419 nm is proportional to the amt. of ascorbic acid in the range of (1.4-28.0) x 10^-7 mole. The relative standard deviations for ten replicate measurements of 1.4 x 10^-6 mole of ascorbic acid was 1.3%. The sample rate of 45 ± 5 sample per h was achieved. The usefulness of the method was tested in the determination of ascorbic acid in fruit juices and vitamin C tablets.
Ascorbic acid Fluorescence Indirect

"Amperometric Differential Determination Of Ascorbic Acid In Beverages And Vitamin C Tablets Using A Flow Cell Containing An Array Of Gold Microelectrodes Modified With Palladium"
Electroanalysis 1998 Volume 10, Issue 13 Pages 887-890
Renato C. Matos, M&aacute;rcio A. Augelli, Jairo J. Pedrotti, Claudimir L. Lago, L&uacute;cio Angnes

Abstract: A simple and attractive method for quantification of ascorbic acid (AA) in beers, soda, natural juices, and commercial vitamin C tablets was developed by combining flow injection analysis and amperometric detection. An array of Au microelectrodes electrochemically modified by deposition of Pd was employed as working electrode which was almost unaffected by fouling effects. AA was quantified in beverages and vitamin tablets using amperometric differential measurements. The method is based on three steps involving the flow injection of the sample plus a standard addition of AA, of the pure sample, and of the enzymatically-treated sample. The enzymatic treatment was carried out with Cucumis sativus tissue, which is a rich source of ascorbate oxidase, at pH 7. The calibration plots for freshly prepared AA standards were linear in the concentration. range of 0.18-1.8 mg/L with a relative standard deviation (RSD) <1%, while for real samples the deviations were 2.7-8.9%.
Ascorbic acid Amperometry Electrode Electrode Differential detection Standard additions calibration Enzyme

"Electrochemistry Of Ascorbic Acid At Polypyrrole-dodecyl Sulfate Film-coated Electrodes And Its Application"
J. Electroanal. Chem. 1994 Volume 365, Issue 1-2 Pages 197-205
Zhiqiang Gao*, Beshen Chen and Minxian Zi

Abstract: The voltammetric, amperometric and chronoamperometric behavior of ascorbic acid at such electrodes involved an oxidation peak at ~0 V (vs. SCE), i.e., 300 mV more negative than at an uncoated electrode. The properties of such electrodes were superior to polypyrrole films prepared in solution of inorganic anions. The low oxidation potential rendered the proposed electrodes suitable for the FIA determination of ascorbic acid. The RSD at the 30-50 mg level in single- and multi-vitamin tablets were 5.0%, and recoveries of standard additions to these sample solution were 94-107%.
Ascorbic acid Voltammetry Amperometry Electrode Standard additions calibration

"Highly Sensitive And Selective Determination Of Riboflavine By Flow Injection Analysis Using Parallel Dual-cylinder Micro-electrodes"
J. Electroanal. Chem. 1994 Volume 375, Issue 1-2 Pages 185-192
Wenfeng Peng, Huimei Li and Erkang Wang*

Abstract: Crushed multivitamin tablets were dissolved in 0.02 M acetic acid, and the solution was passed through a glass filter (5-15 µm), diluted to 100 mL with 0.1 M NaHSO3, further diluted tenfold with 0.1 M NaHSO3 and injected (10 µL) into a carrier stream of deoxygenated 0.1 M NaHSO3 (1 ml/min). A diagram of the wall-jet/parallel dual-cylinder micro-electrode cell is presented, and its construction is described (cf. Ibid., 1993, 347, 1). The two electrodes were maintained at -0.4 and 0 V vs. SCE, respectively, so that the current density for the oxidation of the reduced riboflavine was enhanced by 'redox recycling' (cf. Weber and Purdy, Anal. Chem., 1982, 54, 1757). The peak current at 0 V varied linearly up to 70 ng of riboflavine, and the detection limit was 35 pg. For 3.5 and 35 ng of riboflavine, the RSD (n = 10) were 2.8 and 1.7%, respectively. There was little interference; pyridoxine was reduced irreversibly at -0.4 V, and a tenfold excess did not interfere.
Riboflavine Electrode Electrode Amperometry Interferences Dual detection

"Analysis Of Neomycins A, B And C By High Performance Liquid Chromatography With Post-column Reaction Detection"
J. Pharm. Biomed. Anal. 1985 Volume 3, Issue 3 Pages 259-267
J. A. Apffel*, J. Van Der Louw, K. R. Lammers, W. Th. Kok, U. A. Th. Brinkman, R. W. Frei and C. Burgess

Abstract: Powdered tablets were dissolved in 15 mM Na acetate buffer (pH 7) for analysis. Lotions, creams or ointments were mixed with CHCl3 and extracted with buffer solution and the aqueous phase was analyzed. Optimum separation was achieved on a column (15 cm x 4.6 mm) of LiChrosorb RP-2 (5 µm) with a mobile phase of Na dodecyl sulfate (75 mg l-1) - 0.5 M Na2SO4 - 15 mM Na acetate buffer (pH 7) and post-column derivatization with phthalaldehyde - mercaptoethanol and fluorescent detection. The coefficient of variation for neomycins A, B and C were 2.9, 1.8 and 1.5%, respectively, and the detection limits were 0.4 ng for A and 5 ng for B and C.
Neomycin A Neomycin B Neomycin C HPLC Fluorescence Post-column derivatization

"Automated Flow Injection Determination Of Salicylates Using Trinder Reaction For Clinical Analysis, Assays And Dissolution Studies Of Formulations"
J. Pharm. Biomed. Anal. 1988 Volume 6, Issue 1 Pages 35-46
M. A. Koupparis* and P. I. Anagnostopoulou

Abstract: The construction and use of a flow injection analyzer. with absorbance measurement at 540 nm is described. Salicylate(I), salicylamide(II) and methyl salicylate(III), as well as aspirin after alkaline hydrolysis, were determined by reaction with Fe(III) in weakly acidic medium (0.02 M HNO3). The method has been applied to tablets (and lotions) for determination of 25 to 250 or 80 to 800 mg L-1 of I, 30 to 300 mg L-1 of II and 100 to 1000 mg L-1 of III. It was suitable for dissolution tests. The method was also applied to determine I in serum. Recovery was 96.4 to 103.0% and coefficient of variation were <1%. Interference was much reduced compared with that affecting the manual Trinder method.
Salicylate Methylsalicylate Salicylamide Aspirin Clinical analysis Spectrophotometry Dissolution rate Interferences Method comparison

"A Flow Injection System With In-series Ultraviolet And Electrochemical Detection For The Simultaneous Determination Of Lovastatin And Butylated Hydroxyanisole In A Tablet"
J. Pharm. Biomed. Anal. 1988 Volume 6, Issue 3 Pages 271-276
David J. Mazzo*, Stephen E. Biffar, Kimberley A. Forbes, Carrie Bell and Marvin A. Brooks

Abstract: Sample solution (prep. described) was injected (4 µL) into a carrier stream (1.0 mL min-1) consisting of 25 mM NaH2PO4 (adjusted to pH 4.0 with H3PO4) - acetonitrile - methanol (33:55:12). The resulting solution was passed to a photodiode array detector for detection of mevinolin(I) at 254 nm, and then to an amperometric detector for detection of butylated hydroxyanisole(II) at +0.60 V vs. Ag - AgCl. Fouling of the vitreous-carbon working electrode due to oxidation of II resulted in a 50% decrease in sensitivity over 8 h; however, this decrease was insignificant during a typical analysis (30 injections at 4 min-1). Accuracy was within 1 and 4%, respectively, for I and II. Precision was ~1% for I and II (n = 10).
Drugs Lovastatin Mevinolin Butylated hydroxyanisole Amperometry Electrode Spectrophotometry Dual detection

"Flow Injection Extraction Applied To Dissolution Rate Studies Of Felodipine Tablets"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 4 Pages 421-431
L. Nord*, M. Sundgren and A. Torstensson

Abstract: A flow injection analysis (FIA) extraction method has been developed for the analysis of felodipine tablets in connection with dissolution rate testing. The water-soluble oxidation product of felodipine, a pyridine derivative, was extracted into chloroform and measured at 275 nm spectrophotometrically. The FIA-extraction method has been compared with the present liquid chromatographic (LC) method. The sampling rate for the FIA-extraction (60 samples h-1) is 5 times higher than for the LC method. The FIA-extraction method has a standard deviation of 1% for both standards and samples which is the same as for the LC method.
Felodipine Sample preparation Spectrophotometry Extraction Dissolution rate Method comparison Organic phase detection

"Determination Of Erythromycin In Tablets And Capsules Using Flow Injection Analysis With Chemiluminescence Detection"
J. Pharm. Biomed. Anal. 1989 Volume 7, Issue 11 Pages 1281-1285
Neil D. Danielson*, Li He, James B. Noffsinger and Letithia Trelli

Abstract: A flow injection system is described in which erythromycin in the carrier solution reacts at pH 6.0 with tris(bipyridine)ruthenium(III) in the low-volume detector cell, generating a product, the chemiluminescence of which is measured at 600 to 625 nm. The calibration graph is rectilinear from 3 to 24 µg mL-1. The coefficient of variation are 0.7 to 4.6% (n = 5). The method is suitable for combining with HPLC for determination of erythromycin in more complicated matrices.
Erythromycin Chemiluminescence HPLC

"Determination Of Penicillin In Pharmaceutical Formulations By Flow Injection Analysis Using An Optimised Immobilised Penicillinase Reactor And Iodometric Detection"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 1 Pages 49-60
M. A. J. van Opstal, R. Wolters, J. S. Blauw, P. C. van Krimpen, W. P. van Bennekom and A. Bult

Abstract: An automated assay for the determination of penicillin in formulations suitable for use in pharmaceutical quality control is presented. The method is based on the classical iodometric penicillin assay which is incorporated in a flow injection analysis (FIA) system. The required hydrolysis is performed online by using an immobilized penicillinase reactor. Packed-bed and single-bead-string enzyme reactors are compared. It turns out that a packed-bed penicillinase reactor (10 cm x 1.5 mm i.d.) provides complete hydrolysis within short residence time, while only little back-pressure is generated. This enzyme reactor is stable for at least 9 months. Enzymatic hydrolysis of the β-lactam ring results in the formation of the corresponding penicilloic acid, which consumes iodine. The iodine consumption is determined colorimetrically by measuring the decrease of the absorbance of the blue colored iodine/starch complex. The optimum reactor length and flow rate for the colorimetrical detection reaction are determined. The optimized method is applied to the assay of penicillin in formulations and the results are compared with the 'true' results obtained with a reference method: a mercurimetric titration. The reliability of the flow injection method is evaluated quantitatively by determining the maximum total error (MTE). The reliability is shown to be highest when measuring at a 0.3-mM level. Eight formulations including capsules, tablets and injectables containing penicillin G, amoxicillin or flucloxacillin are assayed. The MTE does not exceed the 6% level and the most probable MTE is between 1.5 and 3.5%. A 30 µL portion of aqueous penicillin (I) solution was injected into a carrier stream (0.3 mL min-1) of 0.2 M potassium phosphate buffer (pH 6.5) and pumped into a packed-bed immobilized β-lactamase reactor (10 cm x 1.5 mm). The penicilloic acid formed was passed into a single-bead-string reactor (25 cm x 1.5 mm) and mixed with a reagent stream (0.7 mL min-1) of aqueous 0.15% starch solution - (0.5 mM I in 0.5 mM KI) - phosphate buffer (1:1:3). The decrease in absorbance of the blue iodine - starch complex was measured at 590 nm. The calibration graph was rectilinear from 0.1 to 0.5 mM I; the detection limit was 0.025 mM. Results compared well with those obtained by mercurimetric titration. Results are presented for the determination of I in eight formulations, including capsules, tablets and injectables.
Penicillin Spectrophotometry Optimization Immobilized enzyme Automation Enzyme Titrations Buffer pH Calibration Indirect Method comparison

"Determination Of Subtilisin Proteolytic Activity By Flow Injection Analysis With Fluorescence Detection"
J. Pharm. Biomed. Anal. 1990 Volume 8, Issue 7 Pages 597-601
C. Hayes Powell* and R. Brett Nelson

Abstract: The method is designed to be used primarily for the rapid determination of subtilisin A enzymatic activity in tablets for the cleaning and disinfection of contact lenses. The basic flow injection analysis system consists of a Quik-Chem automated ion analyzer. (Lachat Instruments) and a McPherson model FK750BX fluorescence spectrometer with a deuterium source and modified inlet and outlet tubing connected to the 24 µL flow cell. Test solution was mixed with casein within the system to form fluorescent peptides and amino-acids (particularly tyrosine- and tryptophan-containing residues) which were separated by dialysis from unreacted casein. The calibration graph was based on the comparison of the response of unknown solution with standard subtilisin A solution of known activity run under identical conditions. The effect on the results obtained of varying excipient concentration. (such as Na2CO3, tartaric acid and acetylcysteine) was negligible.
Activity, biological Fluorescence Enzyme Automation Flowcell Dialysis Activity Lachat

"Spectrophotometric Determination Of Promethazine By Flow Injection Analysis And Oxidation By Cerium(IV)"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 1 Pages 37-42
J. Martinez Calatayuda,* and T. Garcia Sanchob

Abstract: Sample was dissolved in 0.2 M H2SO4 and the solution was injected into a carrier stream (4 mL min-1) of 0.303 mM Ce(IV) in 0.2 M H2SO4; the absorbance of resulting colored solution was measured at 514 nm. The calibration graph was rectilinear from 10.3 to 51.3 ppm of promethazine (I); the coefficient of variation (n = 40) was 1.2% for 35 ppm of I. Tolerance limits for interfering compounds are presented. The method was used to determined I in pharmaceuticals. A flow injection analysis (FIA) procedure is proposed for the determination of promethazine. The sample solution is directly injected into the carrier-reagent stream which comprises a solution of ceric ions in a sulfuric acid medium. The absorbance at 514 nm from the red color developed by the oxidation of promethazine is measured. Effects of foreign substances have been investigated and the procedure has been applied to the determination of promethazine in a pharmaceutical formulation (tablets).
Promethazine Spectrophotometry Redox Interferences

"Automation Of Dissolution Testing Of Solid Oral Dosage Forms"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 727-733
E. Lamparter* and Ch. Lunkenheimer

Abstract: An automated dissolution system (AUTO DISS) in which all operating steps are carried out synchronously is described. All steps from the filling of vessels with dissolution medium to cleaning and drying of vessels are controlled by a microcomputer. Up to 20 cycles can be tested in succession with six individual tablets per cycle. Online determination of active ingredient concentration. is possible with the aid of an integrated automatic sampler in combination with various measuring instruments such as UV - vis spectrometry, liquid chromatography or flow injection analysis. The suitability of the system was demonstrated by the dissolution and determination of brotizolam tablets and bepafant capsules using flow injection analysis and diode-array spectroscopy, respectively. Dissolution testing of solid oral dosage forms plays a very important part both in the development of new products and in quality control. A fully automated system for dissolution testing known as AUTO DISS is presented and its components are described. Online determination of active ingredient concentration is possible with the aid of an integrated automatic sampler in combination with various measuring instruments (UV-vis spectrometry, liquid chromatography and flow injection analysis). The suitability of the system is demonstrated by determination of the dissolution of brotizolam from tablets by FIA and of bepafant from capsules by diode-array spectroscopy.
Brotizolam Bepafant Spectrophotometry Process control Dissolution rate Automation

"Determination Of Disodium Clodronate In Bulk Material And Pharmaceuticals By Ion Chromatography With Post-column Derivatization"
J. Pharm. Biomed. Anal. 1992 Volume 10, Issue 10-12 Pages 881-887
Jussi P. Kosonen

Abstract: Portions (25 µL) of bulk materials, injectable preparations, tablets and capsules (prep. described) were analyzed by ion-chromatography, on a column (25 cm x 4 mm) of poly(styrene - divinylbenzene)copolymer (10 µm) in series with a guard column (5 cm x 4 mm) of IonPac AG7 with 40 mM HNO3 as mobile phase (0.5 mL min-1) and detection at 300 nm after post-column derivatization with acidic Fe(III) solution (0.25 mL min-1). Calibration graphs were rectilinear from 0.02 to 0.07 mg mL-1 of Na2 clodronate (I). Recoveries of I were 99.5 and 100.7% for capsule and tablet, respectively. The coefficient of variation (n = 6) were 0.8 to 1.3%.
Clodronate HPIC Spectrophotometry Post-column derivatization

"The Study Of The Differential Pulse Voltammetric Behaviour Of Ergot Alkaloids And Their Determination By DC Amperometric Detection In A FIA System"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 3 Pages 191-196
Judit Inczeffy*, Zsuzsa Bertha Somodi, Zs&oacute;fia Pap-Sziklay and Gyorgy Farsang

Abstract: The ergot alkaloids possess strong pharmacological effects and are important drugs with widespread clinical uses. The ergot alkaloid preparations manufactured by Gedeon Richter Chemical Works Ltd have a very low active substance content (e.g. 1.0 mg in each Secadol (0.4 g) coated tablet); therefore a sensitive method of determination must be used. Because of this constraint the differential pulse voltammetric behavior of ergot alkaloids was studied in respect of the effects of pH and composition of media and an automated FIA system with amperometric detection has been used to develop a selective and sensitive method for the routine quantitative assay of these alkaloids. A short summary is given of the experimental evidence to substantiate the stoichiometric equation proposed for the electrochemical oxidation of the lysergic acid type of ergot alkaloids, the mechanism may be generally applicable for compounds having the ergoloid skeleton. In the course of the work it was concluded that a simple DC amperometric method of detection in a FIA system could be applied to determine the content of ergot alkaloids of different pharmaceutical preparations. A suitable method designed to meet current analytical requirements has been developed and validated. The effects of pH and composition of media on the differential-pulse voltammetric behavior of ergot alkaloids was investigated and an automated flow injection analysis (FIA) system with amperometric detection (illustrated) was developed for their determination. Powdered coated tablets [equivalent to 1 mg of ergotamine tartrate (I) and 100 mg of caffeine] were dispersed in water (2 ml) and diluted to 50 mL with carrier solution A portion (1 ml) of this solution was further diluted to 10 mL with carrier solution A 60 µL-portion of solution was injected into a carrier stream (0.5 mL min-1) of acetonitrile - 0.02 M KH2PO4 (1:1; pH 2) followed by DC amperometric detection. The detection limit and quantitation limit of I were 0.037 and 0.12 µg mL-1, respectively. The method may be applied in the determination of other ergot alkaloids.
Alkaloids, ergot Voltammetry Amperometry

"Determination Of Penicillamine Or Tiopronin In Pharmaceutical Preparations By Flow Injection Analysis"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 8 Pages 633-638
M. S. Garcia, C. Sanchez-Pedre&ntilde;o*, M. I. Albero and V. Rodenas

Abstract: Powdered tablets were dissolved in water and the solution was filtered. Portions (70 µL) of the filtrate were injected into a carrier stream of water which merged with stream of 1 mM PdCl2 in 1 M HCl for determination of penicillamine (I) or a stream of 0.5 mM PdCl2 in 0.25 M HCl for determination of tiopronin (II). The mixture passed though a reaction coil (180 cm long for I and 90 cm long for II) and the absorbance was measured at 400 nm. Flow rates were 1.2 and 2.2 ml/min for the determination of I and II, respectively. Calibration graphs were rectilinear for 0.01-0.7 mM I and for 0.01-0.6 mM II. RSD (n = 10) for 0.17 mM I and 0.5 mM II were 0.8 and 0.3%, respectively. The method was sufficiently selective, and there were no significant differences between the labelled contents and the obtained results for both drugs. Two flow injection analysis (FIA) methods, using spectrophotometric detection, are proposed for the determination of penicillamine or tiopronin [N-(2-mercaptopropionylglycine)]. The procedures are based on the formation of yellow complexes between these thiol-containing drugs and Pd(II), in a 1 M or 0.25 M HCl medium, respectively. With peak height as a quantitative parameter, penicillamine is determined over the range 1.0 x 10^-5-7.0 x 10^-4 M; for tiopronin the range is 1.0 x 10^-5-6.0 x 10^-4 M. The methods have been applied to the routine determination of the drugs in pharmaceutical preparations.
Penicillamine Tiopronin Drugs Sample preparation Spectrophotometry Complexation

"Flow Injection Spectrophotometric Determination Of Piroxicam"
J. Pharm. Biomed. Anal. 1993 Volume 11, Issue 10 Pages 933-938
C. S&aacute;nchez-Pedre&ntilde;o*, M. S. Garcia, M. I. Albero and J. Rodriguez

Abstract: Methanolic sample solution was injected into a carrier stream of methanol (1.2 ml/min) which merged with a stream of methanolic 0.1 M HCl and passed through a reaction coil (70 cm long) before detection at 332 nm. Alternatively, the carrier stream merged with a stream of methanolic 5 mM Fe(III); in this instance, detection was at 520 nm. Calibration graphs were linear for 0.15-15 and 30-500 µg/ml of piroxicam with use of detection at 332 and 520 nm, respectively; corresponding detection limits were 0.15 and 7.5 µg/ml. Recoveries were >98% for the two methods, and sample throughput was 90/h. The method was used to analyze suppositories, tablets, capsules, creams and ampoules. Two flow injection analysis (FIA) methods are proposed for the determination of piroxicam. The first involves measurement of the UV absorbance of a solution containing the drug, methanol and hydrochloric acid at 332 nm; in the second method a Fe(III)-piroxicam complex is formed in a methanolic medium and the absorbance is measured at 520 nm. In both methods, the peak height is used as a quantitative parameter and piroxicam is determined over the ranges 0.5-15 and 30-500 µg mL-1, respectively. The methods have been applied to the routine determination of the drug in dosage forms.
Piroxicam Spectrophotometry Complexation

"Determination Of Papaverine And Cocaine By Use Of A Precipitation System Coupled Online To An Atomic Absorption Spectrometer"
J. Pharm. Biomed. Anal. 1994 Volume 12, Issue 2 Pages 179-184
Marcelina Eisman, Mercedes Gallego and Miguel Varcarcel*

Abstract: In the reversed flow injection system (diagram given) incorporating an AAS instrument operated at 357.9 nm, portions (30 µL) of the precipitating reagent, aqueous 0.2% (for papaverine; I) or 0.25% (for cocaine; II) Reinecke's salt of pH 5, was injected into a stream (3.3 ml/min) of 10 mM HCl and passed through a reaction coil (130 cm x 0.5 mm i.d.) producing a high Cr peak. Samples of I or II in 10 mM HCl were then continuously pumped into the system and another injection of Reinecke's salt produced a precipitate which was retained on the filter producing a low peak. The difference between the two peaks represented the amount of precipitated Cr (proportional to the drug concentration). The calibration graphs were linear from 5-85 µg/ml of I and 50-850 µg/ml of II; the corresponding detection limits were 2 and 25 µg/ml and the corresponding RSD were 1.3% and 3.2%. Sample throughput was 150/h. Tolerated amounts of foreign drugs are tabulated. The method was applied to powdered tablets (0.4 or 3 g), oral drops (0.8 ml), syrup (20 ml) and an ampoule of injectable solution dissolved in 100 or 250 mL of H2O.
Papaverine hydrochloride Drugs Spectrophotometry Precipitation Reverse

"Determination Of Diclofenac Sodium, Famotidine And Ketorolac Tromethamine By Flow Injection Analysis Using Dichloronitrophenol"
J. Pharm. Biomed. Anal. 1994 Volume 12, Issue 3 Pages 343-346
B. V. Kamath*, K. Shivram and A. C. Shah

Abstract: Powdered tablets equivalent to 50 mg of diclofenac sodium (I) or 30 mg of famotidine (II) or ketorolac tromethamine (ketorolac trometamol; III) were dissolved in methanol and filtered; injection solution of I were diluted with methanol. Portions (40 µL) of the samples were injected into a carrier stream (0.6 ml/min) of methanol which merged with a stream (0.8 ml/min) of 0.02% 2,4-dichloro-6-nitrophenol in methanol and passed through a reaction coil (2 m x 0.8 mm i.d.) before the absorbance was measured at 450 nm. The calibration graphs were linear for 5-50 µg/ml of I, 10^-80 µg/ml of II and 10^-120 µg/ml of III. The recoveries of I, II and III were 98.31-100.6%, 98.64-100.5% and 98.23-99.86%, respectively, and the RSD were 1.6%. Sample throughput was 40/h. The results agreed well with those obtained by HPLC. Paracetamol interfered with the determination of I. Diclofenac sodium, famotidine and ketorolac tromethamine were determined by flow injection analysis (FIA) with spectrophotometric detection. The sample solutions (5-50 µg mL-1 of diclofenac sodium, 10^-80 µg mL-1 of famotidine and 10^-120 µg mL-1 of ketorolac tromethamine) in methanol were injected into a flow system containing 0.01% (w/v) of 2,4,dichloro-6-nitrophenol (DCNP) in methanol. The color produced due to the formation of a charge transfer complex was measured with a spectrophotometric detector set at 450 nm. A sampling rate of 40 per hour was achieved with high reproducibility of measurements (RSD below 1.6%). The FIA method was applied to the determination of diclofenac sodium, famotidine and ketorolac tromethamine in pharmaceutical formulations.
Diclofenac Famotidine Ketorolac tromethamine Spectrophotometry Method comparison Interferences

"Automated Analytical Systems For Drug Development Studies. 3. Multivessel Dissolution Testing System Based On Microdialysis Sampling"
J. Pharm. Biomed. Anal. 1995 Volume 13, Issue 10 Pages 1235-1241
Ketan P. Shah, Ming Chang and Christopher M. Riley*

Abstract: An automated system consisting of a six-vessel dissolution apparatus, microdialysis sampling, STT E6 multiposition switching valve and a liquid chromatograph was assembled to measure dissolution profiles of immediate and sustained-release tablets. A DL-5 microdialysis loop probe (BAS, Inc.) was immersed in each dissolution vessel and perfused with a suitable medium for sampling. The dialystate from each vessel was injected sequentially onto an online liquid chromatography (LC) system for automated analysis; The STT E6 multiposition switching valve was used to sample up to six vessels simultaneously. After addressing issues related to sample carry-over and between-probe variability; the automated system was used in a reproducible manner (RSD < 3%) to measure the dissolution of immediate-release acetaminophen tablets and Accutrim(R) (containing 75 mg phenylpropanolamine HCl) 16h Precision Release™ tablets. An uneven injection time sequence was used to monitor three acetaminophen tablets per dissolution run using the automated system and each vessel was sampled about every 6.5 min. However, with Accutrim(R) 16 h Precision Release™ tablets, a longer sampling interval (10 min) was used, the six tablets could be tested in each dissolution run. The dissolution profiles of acetaminophen and Accutrim(R) tablets measured using the automated multivessel dissolution system compared well with manual and automated single-vessel dissolution systems. 3 references.
Acetaminophen Phenylpropanolamine LC Dissolution rate Dialysis

"FIA Titrations Of Ephedrine In Pharmaceutical Formulations With A PVC Tetraphenylborate Tubular Electrode"
J. Pharm. Biomed. Anal. 1995 Volume 13, Issue 4-5 Pages 459-464
Manuel N. M. P. Al&ccedil;ada, Jos&eacute;L. F. C. Lima and M. Concei&ccedil;&atilde;o B. S. M. Montenegro*

Abstract: To prepare membranes for the tubular electrodes, 25 mL 0.1 M sodium tetraphenylborate were mixed with 20 mL 0.1 M tetrapentylammonium bromide in acetone, and the acetone was evaporated. The resulting crystals (0.06 g) were dissolved in 2.42 g 2-nitrophenyl-phenyl ether and portions (0.4 ml) of the resulting solution were mixed with 0.18 g PVC. Tubular electrodes were constructed as described previously (Lima et al., J. Flow Injection Anal., 1990, 7, 19) and applied to the flow injection analysis of ephedrine hydrochloride (I) in pharmaceuticals. Liquid samples equivalent to 2.5 mg I were diluted to 25 mL in phosphate buffer of pH 6.3. Powdered tablets equivalent to 12.6 mg I were dissolved in 25 mL phosphate buffer. Portions (80 µL) were injected into a carrier stream (6.8 ml/min) of 0.1 mM sodium tetraphenylborate in phosphate buffer. After passage through a mixing chamber (details given), potentiometric measurements were made vs. an Orion 90-02-00 double-junction reference electrode. The calibration graph was linear from 0.2-2 mM I and the RSD were 1.5%. Sample throughput was 60/h. The mean recovery of I in pharmaceuticals was 98.6% with a RSD of 2.5%. A flow injection system for the titration of ephedrine in pharmaceutical products with potentiometric detection was developed. For this purpose a tetraphenylborate tubular electrode was constructed. The electrode was prepared without inner reference solution and with a PVC membrane based on tetrapentylammonium tetraphenylborate as ion exchanger and 2-nitrophenylphenyl ether as mediator solvent. Its operational characteristics were evaluated in a low dispersion manifold and compared with more conventionally shaped electrodes using the same sensor. In the pH range 2.5-11.5, the electrodes showed linear response between 3.8 x 10^-6 and 0.1 M with a slope of -56.4 mV/log[BPh4]. Ephedrine determinations in pharmaceutical products were carried out in a single channel manifold with a mixing chamber incorporated and using the tubular electrode as detector. Recovery rates of 98.6±2.5% were obtained in the analysis of tablets, nasal drops and syrups with a sampling rate of about 60 h-1.
Drugs Ephedrine hydrochloride Electrode Potentiometry Electrode Mixing chamber Titrations

"Fluorimetric Determination Of Chloroxine Using Manual And Flow Injection Methods"
J. Pharm. Biomed. Anal. 1996 Volume 14, Issue 11 Pages 1505-1511
Tom&aacute;s P&eacute;rez-Ruiz*, Carmen Mart&iacute;nez-Lozano, Virginia Tom&aacute;s and Jos&eacute; Carpena

Abstract: Powdered tablets equivalent to 20 mg chloroxine (5,7-dichloroquinolin-8-ol; I) were shaken with 25 mL 4 M acetic acid, sonicated and diluted to 1 l with water. Topical preparations equivalent to 10 mg I were heated with 25 mL methanol/acetic acid (3:2) and diluted to 1 l with water. For FIA, sample (95 µL) was injected into a stream (1.2 ml/min) of 14 mM sodium lauryl sulfate which was merged with a stream of 0.2 M acetate buffer (0.4 ml/min) of pH 4.2 and then a stream (0.4 ml/min) of 2.5 mM AlCl3. After passing through a reactor coil (60 cm x 0.5 mm i.d.) the fluorescence was measured at 496 nm (excitation at 399 nm). A batch method was also carried out (details given) in which the calibration graph for I was linear for 20 nM- to 51 µM-I and the detection limit was 5 nM. For FIA, the calibration graph was linear for 0.56-56 µM-I, and the detection limit was 0.13 µM. RSD were 2.3% and 0.38% for the batch and FIA methods, respectively. Recoveries were 96-103%.
Chloroxine Fluorescence Method comparison Buffer Method comparison

"Development And Validation Of A Flow Injection Method For The Determination Of Albumin Tannate, The Active Component Of A Pharmaceutical Preparation"
J. Pharm. Biomed. Anal. 1997 Volume 15, Issue 4 Pages 447-452
L. G&aacute;miz Gracia and M. D. Luque de Castro*

Abstract: Powdered tablets (5 mg) were sonicated in aqueous 2.5% NH3 solution for 3 min. A portion (275 µL) was injected into a carrier stream (1 ml/min) of water which merged with a stream (1 ml/min) of aqueous 25% Folin-Ciocalteu reagent and passed through a mixing coil (30 cm x 0.5 mm i.d.). The flow then merged with a stream (1 ml/min) of 1 M NaOH and passed through a second mixing coil (200 cm x 0.5 mm i.d.) before passing to the detector where the reaction product was monitored at 760 nm. The calibration graph was linear for up to 50 mg/l albumin tannate (I) and the mean recovery was 100%. The detection limit was 0.56 mg/l. Sample throughput was 50/h. The intra- and inter-day RSD (n = 10) for 25 mg/l I were 1.17% and 1.76%, respectively. No interference was observed. A flow injection analysis method for the determination of albumin tannate in tablets is reported. After optimization of the variables involved, the method has been characterized and validated in terms of calibration using three procedures: repeatability and reproducibility; ruggedness; and selectivity. Finally, it has been applied to real samples (tablets).
Tannin albuminate Spectrophotometry Detection limit Optimization Interferences Selectivity

"Flow Injection Spectrophotometric Determination Of Frusemide Or Sulfathiazole In Pharmaceuticals"
J. Pharm. Biomed. Anal. 1997 Volume 15, Issue 4 Pages 453-459
M. S. Garc&iacute;a, C. Sanchez-Pedre&ntilde;o*, M. I. Albero and V. R&oacute;denas

Abstract: Powdered tablets equivalent to 40 mg frusemide (I) or 50 mg sulfathiazole (I) were sonicated for 5 min with 0.6 mL and 1 mL 1 M NaOH, respectively, then diluted to 100 mL with water. Injection solutions were dissolved in water. Portions (72 µL) were injected into a carrier stream of water (1.2 ml/min) which merged with a stream (1.2 ml/min) of 3 mM PdCl2 in Britton-Robinson buffer of pH 5 and passed through a reactor (3 m x 0.5 mm i.d.) maintained at 55°C before the absorbance was measured at 410 nm. The calibration graphs were linear for 20-400 µM-I and 50-300 µM-II, the detection limits were 55 µM and 14 µM, respectively, and the RSD were 0.3% and 0.9%, respectively, (n = 10) at 0.2 mM I. The sampling frequency was 50/h. No interference was observed from ethacridine or ephedrine ricinoleate. Results agreed with those obtained by reference methods (spectrophotometry for I and amperometric titrimetry for II). Recoveries were >=98.9%. Two sensitive and fast flow injection spectrophotometric methods are proposed for the determination of frusemide or sulfathiazole based on the formation of colored complexes between these compounds and Pd(II) at pH 5.0 and 55°C. Using the peak height as a quantitative parameter, frusemide or sulfathiazole was determined at 410 nm over the range 2.0 x 10^-5-4.0 x 10^-4 M or 5.0 x 10^-5-3 x 10^-4 M, respectively. The methods were applied to the determination of these sulfonamides in pharmaceuticals.
Frusemide Sulfathiazole Sample preparation Spectrophotometry Detection limit Interferences Method comparison Heated reaction Standard method

"Colorimetric Flow Injection Determination Of Resorcinol-type β2-adrenergic Drugs With Phenanthro[9,10-d]imidazole-2-chloroimide"
Anal. Sci. 1989 Volume 5, Issue 5 Pages 513-516
S. TANABE, T. TOGAWA and K. KAWANABE

Abstract: For the determination of fenoterol hydrobromide, orciprenaline sulfate or terbutaline sulfate, a portion of ground tablets was extracted with 10 mM HCl (30 ml) by shaking for 10 min. The mixture was diluted with 10 mM HCl to 50 ml, filtered, and the filtrate was diluted 10-fold with water before introduction into the flow injection system; 50 mM borate buffer (pH 11.5) was used as carrier solution (0.8 mL min-1), and reaction with ethanolic 0.003% phenanthro[9,10-d]imidazole-2-N-chloroimide was effected in a 1-m PTFE reaction coil (0.33 mm) at 60°C. Absorbance was measured at 530 nm. Calibration graphs were rectilinear from 0.5 to 200 µM for each drug. Recoveries were >99%; the coefficient of variation (n = 10) were better than 2%. The method was also applied to injection solution and syrup.
Drugs Fenoterol hydrobromide Orciprenaline sulfate Terbutaline sulfate Sample preparation Spectrophotometry Heated reaction Optimization

"Application Of Super Modified Simplex Optimization To The Flow Injection Spectrophotometric Determination Of Promethazine Hydrochloride In Drug Formulations"
Anal. Sci. 1992 Volume 8, Issue 6 Pages 841-843
S. M. SULTAN and F.-E. O. SULIMAN

Abstract: The flow injection system described earlier [Analyst (London), 1991, 116, 177) was applied to the determination of promethazine hydrochloride by using Ce(IV) in H2SO4 medium to oxidize promethazine hydrochloride to a reddish product having maximum absorption at 515 nm. Reaction coil length, Ce(IV) and H2SO4 concentration and flow rate were optimized by the super modified simplex procedure. The max. sampling frequency was 200 h-1 and the calibration graph was rectilinear for 60 to 200 ppm of promethazine hydrochloride. The coefficient of variation for standard solution was 0.8%. The results on tablet and syrup formulations were as accurate as those obtained by the BP method. An accurate, reproducible, flow injection spectrophotometric method for the assay of promethazine was developed using cerium(IV) as an oxidant. The super modified simplex program was utilized for the optimization of dependant parameters. In the method, a 110 µL drug sample was injected into a flowing stream of 6.19 x 10^-4 M cerium(IV) dissolved in 0.512 M H2SO4. The reaction takes place in a reaction coil 62 cm long. Finally, the colored oxidized form of the drug was monitored at 515 nm. Promethazine in the range 60-200 ppm with a 200-sample/h throughout was determined, 0.80% relative standard deviation being attained. The method was successfully applied to the determination of promethazine in proprietary drugs, its accuracy was statistically compared with the British Pharmacopeia official method.
Promethazine hydrochloride Spectrophotometry Optimization Modified simplex Method comparison Standard method

"Determination Of Vitamin D3 And D2 In Multi-vitamin Tablets By High Performance Liquid Chromatography - Atmospheric Pressure Chemical-ionization Mass Spectrometry"
Anal. Sci. 1994 Volume 10, Issue 3 Pages 457-460
T. ADACHI, M. NISHIO, N. YUNOKI, Y. ITO and H. HAYASHI

Abstract: Powdered multi-vitamin tablets equivalent to ~200 iu of vitamin D2 or D3 were spiked with 5 µg of vitamin D2 or D3 as appropriate (internal standard), dispersed in 10 mL of aqueous 50% methanol (1:1) and extracted three times with 15 mL of hexane. The organic phase was evaporated to dryness under vacuum and redissolved in 1 mL of aqueous 90% methanol. Portions (20 µL) were analyzed on a column (15 cm x 4 mm i.d.) of TSK-gel ODS 80 (5 µm) with aqueous 90% methanol as mobile phase (1 ml/min) and atmospheric pressure (AP) CIMS in the selected ion monitoring mode (details given). The calibration graphs for vitamins D2 and D3, 1α-hydroxy-vitamin D3, 25-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 were linear from 150-30 000 ng/ml and the detection limits were ~0.5 ng; the RSD were 1.9-5.7%. The results agreed with those obtained by HPLC with UV detection (details given). Flow injection AP CIMS with a flow rate of 2 ml/min and reduced amounts of sample also gave satisfactory results.
Vitamin D3 Vitamin D2 HPLC Spectrophotometry Mass spectrometry

"Micelle Enhanced Spectrofluorometric Determination Of L-ascorbic-acid Based On Laccase-linked Coupling Reaction Using Flow Injection Stopped-flow Technique"
Anal. Sci. 1997 Volume 13, Issue suppl Pages 67-70
HOUPING HUANG, RUXIU CAI, TAKASHI KORENAGA, XINXIANG ZHANG, YI YANG, YUMIN DU, and YUN'E ZENG

Abstract: A novel spectrofluorimetric method for determination of L-ascorbic acid is described. It is based on the inhibition of L-ascorbic acid on the formation df 2,3-diaminophenazine, which is an oxidation product of o-phenylenediamine catalyzed by laccase, in the presence of Brij-35, which shows strong enhancement on the fluorescence(at lambda em/lambda ex=530 nm/430 nm) of the product, while no effect on the laccase-catalyzed reaction. The mechanism of o-phenylenediamine oxidation reaction catalyzed by laccase in the presence of L-ascorbic acid is discussed. L-ascorbic acid is determined in the range of 0.02 similar to 2.0 µg/ml with a detection limit of 0.014 µg/ml. The method is applied to the determination of L-ascorbic acid in pharmaceuticals, the results agree well with the nominal values and those obtained by the reference method. 20 References
l-Ascorbic acid Fluorescence Catalysis Detection limit Enzyme Method comparison Redox Standard method Micelle Stopped-flow

"Chemiluminescence Detection Of A Benzodiazepine"
Anal. Proc. 1989 Volume 26, Issue 11 Pages 368-369
Anthony R. J. Andrews, Alan Townshend

Abstract: Seven benzodiazepines (concentration. 1 mM) were examined for chemiluminescence in a flow injection system with various oxidizing and reducing reagents and water as carrier. Only loprazolam (I), with acidic KMnO4 as reagent, gave a measurable response. Optimum conditions for the determination of I were; water as solvent, 0.94 M formic acid, adjusted to pH 0.9 with HCl, as carrier, 0.2 mM KMnO4 as reagent, and a flow rate of 1.3 mL min-1 in the sample and reagent lines. The calibration graph was rectilinear from 0.01 to 5 mM I, and the detection limit was 7 µM. Of 12 metal ions examined, only Fe(II) and Mn(II) interfered. The method could be used to determine I in tablets; excipients did not interfere.
Loprazolam Benzodiazepine, derivatives Chemiluminescence Optimization pH Calibration Interferences Detection limit Redox

"Flow Injection Analysis Of Pharmaceutical Compounds. 5. Quantitative Determination Of Stilboestrol Phosphate (fosfestrol) In Ampoules And Tablets"
Acta Pharm. Fenn. 1989 Volume 98, Issue 4 Pages 247-251
Abdel Moety, E.M.;El Khateeb, S.Z.

Abstract: Fosfestrol (5 to 30 µg mL-1) was determined at ~239 nm with water as carrier stream (2.2 mL min-1). The coefficient of variation (n = 6) were ~0.1 to 0.2%, and the sampling rate was ~140 h-1. The method was applied to ampoules and tablets. (For Part IV see Anal. Abstr., 1988, 50, 4E85).
Drugs Fosfestrol

"Development Of A Flow Injection Method Based On Bromimetry And Iodimetry For The Determination Of Medicinal Drugs Such As Isoniazid And Ascorbic Acid"
Bunseki Kagaku 1994 Volume 43, Issue 7 Pages 505-509
Goto, M.;Akabori, K.;Maeda, S.

Abstract: The sample (0.1 ml) is injected into a carrier stream of water (0.2 ml/min) that then merges with already-mixed (in a 50 cm x 0.5 mm coil) streams of KBrO3/KBr (or KIO3/KI) and H2SO4. After being mixed in a 2 m x 0.5 mm coil the combined streams are mixed with a stream of basic ferrocyanide solution in a further 2 m x 0.5 mm coil before amperometric detection of Fe(III) at -0.40 V vs. Ag/AgCl. Results for isoniazid in tablets, Na2S2O3 in injection solution and ascorbic acid also in injection solution agreed reasonably with those obtained by the Jap. P. methods. The throughput was 30 samples per h.
Ascorbic acid Isoniazid Amperometry

"Quinine Determination In Some Mass Produced Pharmaceuticals By Flow Injection Analysis With Fluorimetric Detection"
Cesk. Farm. 1987 Volume 36, Issue 5 Pages 201-206
Polasek, M.;Karlicek, R.;Solich, P.

Abstract: Portions (120 µL) of a solution of quinine sulfate in 0.05 M H2SO4 were injected in a carrier stream of water (1.5 mL min-1), and the fluorescence of the solution was measured at 415 nm (excitation at 365 nm) in a flow cell (volume 2 to 8 µL). Response was rectilinear for 0.05 to 0.3 or 0.5 to 3.0 µg mL-1 of quinine sulfate. The method was applied to dragees and tablets. The coefficient of variation was <1.3% (n = 3).
Quinine Fluorescence Review

"Fluorimetric Determination Of Ergotamine In Medicinal Preparations By Flow Injection Analysis"
Cesk. Farm. 1989 Volume 38, Issue 1 Pages 1-5
Polasek, M.;Solich, P.;Karlicek, R.

Abstract: Samples (~100 µL) of ergotamine tartrate (I) solution in aqueous 2% tartaric acid were injected into a carrier stream of water (1.1 mL min-1) at up to 70 samples h-1. Detection was by fluorimetry at 415 nm (excitation at 325 nm). The calibration graph was rectilinear for 0.1 to 15 µg mL-1 of I. I was determined in tablets (0.3 to 1 mg) and in drops (0.25 mg mL-1). The coefficient of variation was 1.8% (n = 3). Caffeine (100-fold excess) and phenobarbitone (saturated solution in aqueous 2% tartaric acid) interfered.
Ergotamine tartrate Fluorescence Interferences

"Determination Of Dichloroquinolinol In Tablets By Flow Injection Analysis"
Ceska Slov. Farm. 1998 Volume 47, Issue 5 Pages 229-232
Dolejsova, J.;Karlicek, R.;Pospisilova, M.

Abstract: The yellow product of 5,7-dichloro-8-quinolinol reaction with 3-methyl-2-benzothiazolone hydrazone (MBTH) and Ce(IV) was determined by flow injection analysis with spectrophotometric detection at 580 nm. After finding the optimal analytical conditions, dichloroquinolinol could be assayed in the range of 5-26 mg/L with a relative standard deviation of 0.82% at 16 mg/L (n = 10). About 75-80 analyzes could be done per hour. The method was used for the quantitative determination of dichloroquinolinol in the coated tablets Endiaron (Leciva, Praha).
5,7-Dichloro-8-quinolinol Spectrophotometry Optimization

"Electrochemical Derivatization Of Thiamine In A Flow Injection System-application To Thiamine Analysis"
Chem. Pharm. Bull. 1983 Volume 31, Issue 10 Pages 3589-3594
Kusube, K.;Abe, K.;Hiroshima, O.;Ishiguro, Y.;Ishikawa, S.;Hoshida, H.

Abstract: The method is based on electrochemical oxidation of thiamine to thiochrome. A flow-through electrolytic cell, consisting of a vitreous-carbon tube (10 cm x 5 mm) as working electrode and a vitreous-carbon rod (15 cm x 3 mm) as counter-electrode, is described and illustrated. For determination of thiamine, the sample (10 µg mL-1 in methanol) was injected into a flow (0.5 mL min-1) of aqueous 90% methanol 0.05 M in NaClO4 and containing 1% NaOH, and a potential of +0.4 V was applied vs. silver - AgCl. Detection was by fluorimetry at 430 nm, with excitation at 375 nm. The calibration graph was rectilinear for 1 to 100 ng of thiamine and the time required was 3 min for each determination. The results for analysis of a vitamin capsule, a tablet and a syrup were in good agreement with those obtained by a chemically induced fluorimetric and a HPLC method, without interference from other B-group vitamins or a number of other vitamins.
Thiamine Electrode Fluorescence Potentiometry Interferences

"Widely Applicable Electrode Sensitive To Basic Drugs Based On Poly(vinyl Chloride) Membrane Plasticized With Tricresyl Phosphate"
Chem. Pharm. Bull. 1993 Volume 41, Issue 6 Pages 1123-1126
Suzuki H, Nakagawa H, Mifune M, Saito Y

Abstract: An electrode, responsive to many basic drugs, comprised a layer of PVC (29%) and tricresyl phosphate plasticizer (71%) deposited on a PTFE membrane filter. This electrode (0.1 M LiCl as internal reference solution) was used for potential measurements vs. an Ag/AgCl double-junction reference electrode, with the drugs dissolved in acetate buffer of pH 4. A near-Nernstian response (53.0-59.4 mV/decade) was observed for e.g., chlorpromazine, trihexyphenidyl (I), imipramine, dibucaine, papaverine, propranolol, tetracaine, trazodone (II), as their hydrochlorides, and quinidine with a linear range of 0.01-10 mM. Electrode equilibration took only 1-2 min. Inorganic ions and pharmaceutical excipients did not interfere with the determination. The average recovery of II was 99.4% (mean standard deviation 0.7%) over the range 50-3000 µg/ml. Results obtained for I and II in tablets, agreed well with those from a reference method. The electrode may be useful as a detector for flow injection and HPLC analysis.
Trihexyphenidyl Trazodone Electrode HPLC Detector Method comparison Interferences

"Determination Of Captopril Tablets And Their Dissolution By Flow Injection Analysis"
Zhongguo Yiyao Gongye Zazhi 1994 Volume 25, Issue 1 Pages 23-25
ZHANG Shao-Hui;LIU Qan;SHUN Ling-Ling;YU YongMing

Abstract: Captopril tablets and their dissolution were determined by FIA with sodium nitroprusside in the buffer solution (pH 12). In the concentration of range of 20-90 µg/mL, the regression equation of the concentration C with the peak height H was C = 1,002 x 10^-5H + 15.49, r = 0.99991). The recovery was 99.7% for 60 µg/ml (RSD = 0.67%, n = 5). This method is rapid and very sensitive.
Captopril Spectrophotometry Dissolution rate Buffer

"Automated Dissolution Testing With Flow Injection Analysis. Dissolution Profiles For The Antiviral Drugs, DHPG And Acyclovir, In Capsule Formulations"
Drug Dev. Ind. Pharm. 1987 Volume 13, Issue 1 Pages 39-56
Richard A. Kenley, Stuart E. Jackson, Gary C. Visor, and John S. Winterle

Abstract: We have designed, assembled, and tested an automatic dissolution apparatus using flow-injection analysis (FIA) techniques with spectrophotometric detection. The components (pumps, switching valves, detector, and so forth) that comprise the system are all readily-available items used primarily for high-performance liquid chromatography. The system performs well as evidenced by the usual tests for precision, response linearity, and dissolution behavior of standard U.S.P. calibrator (salicylic acid and prednisone) tablets, and offers siqnificant advantages over conventional continuous-flow dissolution testing methods with respect to simplicity, cost, and versatility. Dissolution tests on capsules of the antiviral drugs, DHPG and acyclovir, showed very similar drug release profiles for both formulations.
Drugs DHPG Acyclovir Spectrophotometry Dissolution rate

"Automation Of The Analysis Of Some Active Ingredients In Single-dose, Solid, Oral Drug Products"
Drugs Made Ger. 1986 Volume 29, Issue 1 Pages 53-60
Kubin, H.;Brehm, M.;Ulmen, J.

Abstract: The combination of a solid-sampling device with a HPLC system and a continuous-flow system enabled single tablets to be analyzed automatically from their initial preparations. Simultaneous HPLC and continuous-flow analyzes of products containing phenothiazine derivatives, ergotamine tartrate (I) or codeine were carried out. Results of single dose analyzes on products containing low I concentration. revealed quality deficiencies. All other mixtures satisfied the content uniformity requirement of the USP XX.
Ergotamine tartrate Phenothiazine, derivatives Codeine HPLC

"Electrochemical FIA System Combined With An Immobilized Enzyme Reactor For The Determination Of Ascorbic Acid"
Ernaehrung 1993 Volume 17, Issue 11 Pages 605-608
Friedrich, O.;Sontag, G.;Pittner, F.

Abstract: A simple and rapid method for determination of ascorbic acid (I) was developed by combining an FIA system with an enzyme reactor (L-ascorbate oxidase), an inactive reactor and an amperometric detector. If a sample containing I and another oxidizable substance are 1st passed through the inactive reactor both of them will be detected at +0.7 V. If the same sample is then passed over the enzyme reactor ascorbic acid is oxidized enzymatically and the detector detects only the other oxidizable substance. The difference of the signals is proportional to the concentration. of the I. In juices and lemonades 4.1/20.2 mg/L were found. Pharmaceutical preparations contained 20-497.2 mg/tablet. The relative standard deviation was 0.9-11.7%. (SFS)
Ascorbic acid Electrochemical analysis Immobilized enzyme Reactor

"Spectrophotometric Determination Of Ascorbic Acid In Vitamin C Tablets, Beverages, Orange And Urine With 2,6-dichloroindophenol By Flow Injection Analysis"
Fenxi Huaxue 1991 Volume 19, Issue 2 Pages 182-184
Ma, H.C.;Feng, J.Z.;Cao, B.

Abstract: Sample is injected into a carrier stream of potassium hydrogen phthalate buffer of pH 3.6 (2 mL min-1) for reaction with a reagent stream of 0.2 mM dichloroindophenol (1.5 mL min-1) in a 15-cm reaction coil before kinetic spectrophotometric detection at 525 nm. For the analysis of vitamin C tablets, oranges, beverages and urine by use of the standard-additions method, recovery was 72 to 117%. For 50 µg mL-1 of I, the coefficient of variation was 0.5%. Detection limit was 0.5 µg mL-1. The calibration graph was rectilinear up to 50 µg mL-1. Interference was observed from Fe(III); most co-existing ions (e.g., Zn and Cu), sugars, amino-acids and organic acids (such as citric acid) did not interfere.
Ascorbic acid Spectrophotometry Buffer Interferences Kinetic Standard additions calibration

"Determination Of Ascorbic Acid In Pharmaceutical Products By Flow Injection Spectrophotometry With Iron(III) - 1,10-phenanthroline"
Fenxi Huaxue 1992 Volume 20, Issue 2 Pages 193-195
Fu, L.;Ren, Y.

Abstract: Vitamin C injection was diluted with water, before injection into a flow injection analyzer. and mixing with a reagent stream of pH ~3 at 2 mL min-1 for reaction in a reaction tube with detection at 508 nm. The reagent was prepared from 0.16 g of NH4Fe(SO4)2, 1 mL of 0.8 M H2SO4, 0.1982 g of 1,10-phenanthroline and water to 100 ml, with dilution of 2 mL of the solution to 25 mL with water. Quantitation was by the standard-additions method. Recovery was 92 to 103%; the coefficient of variation (n = 11) were 0.5%. The calibration graph was rectilinear up to 16 µg mL-1 of ascorbic acid. Only Cu(II) interfered seriously. The method was also applied to vitamin C tablets and compound vitamins with a sampling rate of 60 h-1.
Ascorbic acid Spectrophotometry Interferences Standard additions calibration

"Study On The Application Of Photochemical Reactions To A Flow Injection Analysis System. 4. Determination Of Ascorbic Acid Based On The Photochemical Reduction Of Methylene Blue"
Fenxi Huaxue 1995 Volume 23, Issue 2 Pages 187-190
Liu, R.M.;Liu, D.J.;Sun, A.L.;Liu, G.H.

Abstract: A flow injection system (diagram given) was used to determine ascorbic acid (I) based on the chemiluminescent reaction with methylene blue (II). The carrier stream of water was pumped at 1 ml/min and 40 µg/ml of II was pumped at 0.5 ml/ml. Sample was dissolved in 0.1 M HClO4 and buffered with 0.1 M potassium hydrogen phthalate solution of pH 3.4. The sample solution (300 µL) was injected into the carrier stream and the solutions were mixed by passage through a reaction tube (150 cm length). The absorbance was measured at 666 nm. The calibration graph was linear from 0.12-5.6 µg/ml of I. The RSD (n = 11) for 1, 2 and 4 µg/ml of I were 0.92, 0.76 and 0.41%, respectively. The method was used to determine I in its tablets, results agreed with those obtained by indophenol titrimetry. There was no interference from tablet excipients.
Ascorbic acid Spectrophotometry Interferences Method comparison

"Study On The Photochemical Fluorimetry Of P-substituted Phenols"
Fenxi Huaxue 1995 Volume 23, Issue 8 Pages 870-874
Wang, D.Y.;Xu, J.G.;Guo, X.Q.;Zhao, Y.B.

Abstract: A sample was injected (3 ml/min) in to a flow injection photochemical fluorimetry system (diagram shown) and carried to a PTFE reaction tube (6 m x 0.5 mm i.d.) which had a 15 W UV lamp. Fluorescence was measured at 425 nm (excitation at 325 nm). Using this system in situ, p-hydroxyphenylacetic, p-hydroxyphenylpropanoic, homovanillic, and p-methylphenylic acids were determined. Their fluorescence in Na2CO3/NaOH medium increased by up to 5-fold (compared to NaOH medium); detection limits were 2.3-4.8 ng/ml. The method was applied to the analysis of paracetamol tablets; recoveries were 92.7-102%.
p-Hydroxyphenylacetic acid p-Hydroxyphenylpropanoic acid Homovanillic acid p-Methylphenylic acid Fluorescence Photochemistry UV reactor

"Spectrophotometric Determination Of Trace Iodide By Flow Injection Analysis"
Fenxi Huaxue 1996 Volume 24, Issue 6 Pages 720-723
Wang, P.;Shi, S.J.

Abstract: Portions of standard iodide (I) solution were injected into a flow injection analyzer. (schematic shown) and treated with a mixture of 1% bromine and 2% H3PO4 in water in a reaction coil (5 cm x 0.7 mm i.d.). The mixed solution was treated with aqueous 6% sulfosalicylic acid in a second coil (94 cm x 0.7 mm i.d.) and the absorbance of the colored product formed was measured at 580 nm. The calibration graph was linear up to 1 mg/l I. The RSD was 3.3%. Sampling frequency was 80 runs per h. There was little interference. The method was applied to the analysis of iodine-containing tablets, table salt, animal feed and kelp, with recovery of 90-97.5%.
Iodide Spectrophotometry Interferences

"Flow Injection Photochemical Spectrophotometric Determination Of Chlorpromazine In Pharmaceutical Preparations"
Fenxi Huaxue 1997 Volume 25, Issue 5 Pages 573-575
Zhu, J.P.;Chen, H.W.;Fang, Q.J.

Abstract: Sample from chlorpromazine hydrochloride (I) injection solution was diluted with water to a concentration of 12.5 mg/l. A 2 mL portion of the diluted solution was treated with 1 mL 0.1 M HCl and the solution was diluted to 25 mL with water. Portions (250 µL) were injected a carrier stream of water at 2.1 ml/min in a flow injection manifold (diagram illustrated). The stream was carried to a knotted reactor (coiled around a fluorescent lamp) for photochemical reaction by UV irradiation from the lamp at 365 nm. The fluorescence intensity of the reaction product was measured online at 374 nm (excitation at 253 nm). The calibration graph was linear from 10^-600 µg/l of I with a detection limit of 5.4 µg/l. The RSD was 0.5%. No interference was observed from 0.5-fold ascorbic acid and Na2SO3, 100-fold sorbitol and 250-fold glucose. Sampling frequency was 90 runs per h. The method was also applied to the analysis of I in tablets.
Chlorpromazine Fluorescence Interferences Photochemistry Knotted reactor

"Flow Injection Chemiluminescence Determination Of Methotrexate"
Fenxi Huaxue 1998 Volume 26, Issue 9 Pages 1136-1138
He, Y.;Xue, Y.;Feng, M.L.;Lu, J.

Abstract: The chemiluminescence reaction of methotrexate (MTX)-potassium permanganate with formaldehyde as an enhancer was investigated by the flow injection system. A new method for the determination of MTX on the basis of the reaction was reported. The detection limit is 3.4 x 10^-9 g/mL, the relative standard deviation is 1.1% (2.0 x 10^-6 g/mL MTX, n = 11). The linear range is 1.0 x 10^-8 ~ 1.0 x 10^-5 g/mL. The method has been applied to the determination of MTX in the MTX injection and tablet.
Methotrexate Chemiluminescence

"Determination Of Vitamin C By FIA With Reversed Merging Zone"
Fenxi Shiyanshi 1996 Volume 15, Issue 2 Pages 34-36
Huang, Y.S.;Fang, Q.;Huang, J.;Sun, Y.Q.

Abstract: Sample (60-150 µL) was injected into the flow injection manifold (schematic illustrated) and transported by a carrier stream of 0.75 M acetic acid to a merging reactor (1.5 m x 0.5 mm i.d.) and mixed with a reagent stream of 84 µM-KIO3/0.2 M KI. The excess I3- generated by the reaction was detected at 350 nm. The calibration graph was linear up to 50 µM-vitamin C (ascorbic acid; I). Only starch (50 µg), 10 µg Cu(II) and 10 µg Fe(III) interfered. The method was applied to the analysis of canned lychee drinks, fruit cocktail, and I sugar-coated pills, with recoveries of 98.7-99.8% and RSD (n = 5) of 0.5-1.7%.
Ascorbic acid Spectrophotometry Interferences Merging zones

"Determination Of Vitamin B6 By Flow Injection Chemiluminescence Method"
Fenxi Shiyanshi 1998 Volume 17, Issue 3 Pages 5-8
Li, L.;Yang, M.;Feng, M.L.;Lu, J.

Abstract: A new flow injection chemiluminescence method for the determination of vitamin B6 with the system of KMnO4-Na2S2O4-VB6 was established. Strong chemiluminescence signal was observed when the mixed solution of Na2S2O4 and sample was injected into the acidic KMnO4 solution in a flow-cell. The linear range for the determination of VB6 is 1 x 10^-4 ~ 8 x 10^-2 g/L. The detection limit is 5.8 x 10^-8 g/L, the relative standard deviation is 1.1% for 11 measurements of 4.0 x 10^-3 g/L standard solution The recommended method has been successfully used for the determination of VB6 in tablet and injection.
Vitamin B6 Chemiluminescence

"Determination Of Alkylating Antitumor Drugs By Flow Injection Analysis"
Iyakuhin Kenkyu 1987 Volume 15, Issue 5 Pages 749-752
Suzuki, Masao; Nishinaka, Tomoko; Takitani, Shoji (SFS)

Abstract: The alkylating antitumor drugs carboquone, cyclophosphamide, thiotepa, busulfan, and melphalan in commercial preparations (powders, tablets, or injections) were dissolved in suitable solvents and determined by spectrometry with the flow injection system, using 4-(4-nitrobenzyl)pyridine as reactant and detection at 580 nm. This method is simple and fast, and the results are comparable with those from other methods (HPLC, gas chromatography, etc.). (SFS)
Drugs Carboquone Thiotepa Busulfan Melphalan Cyclophosphamide Busulfan Spectrophotometry Method comparison

"Studies On Fluorimetric Determination Of Cyclophosphamide With Nicotinamide And Acetophenone"
Iyakuhin Kenkyu 1985 Volume 16, Issue 5 Pages 1136-1141
Takitani, Shoji; Suzuki, Masao; Takamatu, Motonobu; Murayama, Mitunori; Sano, Akira (SFS)

Abstract: Fluorometric determination of cyclophosphamide (I) [50-18-0] was performed by a manual method and flow-injection anal. with nicotinamide [98-92-0] and acetophenone [98-86-2]. In manual analysis, a 100 mL sample was treated with 500 mL nicotinamide solution (5%(w/v)) at 100°C for 60 min, and the reaction mixture was cooled, mixed with 500 mL acetophenone solution (2%(v/v)) and 500 mL KOH (0.5N in 50% EtOH), allowed to stand for 15 min and treated with 1.5 mL formic acid solution (60%) at 100°C for 3 min for the measurement of the fluorescence intensity (relative to standard quinine solution) at 440 nm with excitation at 385 nm. In the second analysis, a flow-injection system with FP110-type fluorometric detector was used. The calibration curve was linear in the range of 0.02-30 mg/100 mL for the manual analysis and of 0.98-16,000 ng/mL for the flow-injection analysis. The relative standard deviation was 2.37-5.16 and 1.23-3.30%, respectively. The methods were used in the determination of I in pharmaceutical preparations (injections, tablets). The flow-injection method was rapid (20 samples/h) and highly reproducible. (SFS)
Cyclophosphamide Fluorescence Method comparison

"Determination Of Analgin By Flow Injection Analysis With Coulometric Detection"
Izv. Khim. 1991 Volume 24, Issue 1 Pages 118-123
Dakashev, A.D.;Ilcheva, L.I.;Dzambazova, P.

Abstract: Aqueous sample solution was introduced into a stream (0.3 mL min-1) of 0.1 M HCl with a rotation injection valve. In a potentiostatic coulometric detector dipyrone (I) was oxidized on a porous Pt electrode at 0.75 V vs. SCE. ). The method was applied in the analysis of bulk drugs as well as ampoulles and tablets. Recovery was 94.0 to 103.4% of I.
Analgin Coulometry Electrode Electrode

"Amperometric Determination Of Propantheline Bromide In A Flowing Stream At The Glassy [vitreous-]carbon Electrode"
J. AOAC Int. 1985 Volume 68, Issue 2 Pages 165-167
Shah, M.H.;Stewart, J.T.

Abstract: A powdered tablet was washed with ethyl ether and dissolved in the mobile phase [acetonitrile - aqueous 0.05 M NaH2PO4 of pH 6.2 (3:7)]. A 20 µL portion of the solution was injected into a flow cell containing a vitreous-carbon working electrode, a platinum auxiliary electrode and a silver - AgCl reference electrode. The mobile-phase flow rate was 1 mL min-1 and the cell potential was 1400 mV. A calibration graph was rectilinear from 2 to 16 µg mL-1 and the limit of detection was 20 ng. The method showed good accuracy and precision and could be incorporated into automated systems.
Propantheline bromide Amperometry Electrode

"Potential Of Flow Injection Analysis For Dissolution Tests - Application To Online Monitoring Of Tablets With Different Dissolution Rates"
J. Autom. Methods Manag. Chem. 1990 Volume 12, Issue 4 Pages 145-148
J. S. COSANO, A. IZQUIERDO, M. D. LUQUE DE CASTRO, and M. VALC&Aacute;RCEL

Abstract: The possibilities of flow injection analysis for the online monitoring of dissolution tests are illustrated by using a very straightforward manifold to monitor tablets of ascorbic acid dissolving at different rates. The dissolution kinetics can be monitored at an adequate sampling frequency as the method allows up to 90 samples to be processed per h.
Ascorbic acid Dissolution rate Process monitoring

"Comparison Of Capillary Gas-chromatographic Method And Automated Spectrophotofluorimetric Methods For Measuring Content Uniformity Of Conjugated Oestrogens In Pharmaceutical Preparations"
J. Autom. Methods Manag. Chem. 1991 Volume 13, Issue 3 Pages 115-117
J. D. RUSSELL, J. MUMLEY, M. SPRING, A. KUTZ, and R. N. JOHNSON

Abstract: Conjugated oestrogens were extracted from tablets with water, reacted with 0.15% dicyclohexylamine acetate solution in 1,1,2-trichloroethane and extracted into acetic acid - methanol - water (1:1:2) in a flow injection system (Technicon Inc., New York). The complex formed was extracted into hot aqueous 70% H2SO4 and detected at 525 nm (excitation at 415 nm). The coefficient of variation (n = 10) was 2.6%; results compared well with those obtained by GC. Sample throughput was 20 h-1. The cited method has been approved by the FDA.
Estrone sulfate Equilin sulfate Equilenin sulfate GC Fluorescence Sample preparation Automation Extraction Standard method

"Study On The Dissolution Rate Of Acetaminophen Tablets By Flow Injection Analysis"
Zhongguo Yaoke Daxue Xuebao 1988 Volume 19, Issue 4 Pages 294-296
Jiang Xinru, Mei Rongfen and An Dengkui

Abstract: The dissolution rate of acetaminophen(paracetamol) tablets by using flow injection analysis coupled with UV spectrophotometer was studied. The sample solution (102 µL) was injected into the carrier stream, which was a 0.01 mol/L sodium hydroxide solution. Acetaminophen in the range of 2-20 µg/mL can be rapidly determined with a precision of 0.18%. A rate of measurements was 120-180 times per hour. The average recovery of acetaminophen was 100.5±0.37%, and the coefficient of variation was 0.67%. Results obtained by the proposed method were found to be in good agreement with those obtained by the official technique.
Acetaminophen Drugs Spectrophotometry Dissolution rate Method comparison

"Continuous-flow Automated HPLC Analysis Of Fat-soluble Vitamins In Tablets"
J. Chromatogr. Sci. 1978 Volume 16, Issue 12 Pages 616-623
J.W. Dolan, J.R. Gant, N. Tanaka, R.W. Giese and B.L. Karger

Abstract: A prototype automated system involving continuous-flow analysis and high performance liquid chromatography (CFA/ HPLC) has been developed for the analysis of fat-soluble vitamins in individual pharmaceutical tablets. The novel features are the front-end coupling of CFA to HPLC, injection of hexane solutions on reversed phase columns, separation/quantitation of vitamins A, D2 and E within single chromatographic runs for a wide variety of tablets, and a dynamic range sufficient to accommodate the 1000-fold higher levels of vitamins A and E over D2 in the same tablets. The analysis rate is 10 samples per hour, the precision better than 6% for all three vitamins, and the recovery is 70-90% of that obtained by the standard AOAC method. Although the system is a prototype, it already greatly outperforms current manual analyzes which are time consuming, tedious, and demanding in terms of the level of skill and experience of the experimenter. Included in this work are some retention comparisons of commercial columns.
Vitamin A Vitamin D2 Vitamin E HPLC Interface Method comparison

"HPLC Analysis Of An Amino Bisphosphonate In Pharmaceutical Formulations Using Post-column Derivatization And Fluorescence Detection"
J. Chromatogr. Sci. 1990 Volume 28, Issue 11 Pages 563-566
Kwong, E.;Chiu, A.M.Y.;McClintock, S.A.;Cotton, M.L.

Abstract: Monosodium 4-amino-1-hydroxybutane-1,1-diphosphonic acid (MK 217) (in tablets or solution) was diluted or extracted with water and injected into an IONPAC NS1 5 µm column (Dionex) which was packed with a neutral macroporous resin that was stable over the entire pH range. The mobile phase (1 mL min-1) was 10 mM phosphate buffer (pH 8.0) - acetonitrile (3:2) containing 10 mM cetyltrimethylammonium bromide, with post-column derivatization (with o-phthalaldehyde and mercaptoethanol) and fluorimetric detection. The calibration graphs were rectilinear from 0.1 to 10 µg mL-1 and 10 µg mL-1 to 1 mg mL-1 with a detection limit of 100 ng. Within-day and between-day coefficient of variation at the 5 µg mL-1 level were 2% and 7%, respectively.
Monosodium 4-amino-1-hydroxybutane-1,1-diphosphonic acid HPLC Fluorescence Post-column derivatization Column Calibration Detection limit Resin

"A Cyclic Flow Injection System For A Determination Of Thiamine Using A Sensitive Chemiluminescent Detection Associated With Zero Emissions Research Initiative"
J. Flow Injection Anal. 1998 Volume 15, Issue 1 Pages 25-38
Ishii, M.;Kawashima, M.

Abstract: A unique anal. technique going along with a concept of The Zero Emissions Research Initiative (ZERI) announced by The United Nations University in 1995, a cyclic flow injection system with a sensitive chemiluminescent (CL) detection was developed for a determination of thiamine. The present system with much possibility to a recycling for the used CL reagents was consisted of a single manifold and also superior to a sensitivity, a simplicity and an economicity in comparison with a current technique. The CL reaction is initiated by oxidation of thiamine in an alkaline potassium ferricyanide solution and then produces thiochrome of an emitter. The CL was also enhanced until an available level for the determination by the energy transfer to a dye-sensitizer uranine. Anal. figure of merits for the present system was as follows, concerning a use of the standard solution of thiamine. The limit of determination: 2.0 x 10^-5 M, magnitude of the determination: 3, sample frequency: 150 for the 100 mL reagent solution RSD: ~2% in 150 repeated runs of 2.5 x 10^-3 M thiamine, stability of the system: 1 wk at least. The present system was also applicable to a real sample anal. and then could successfully contribute to a concept of the ZERI, too.
Thiamine Chemiluminescence Reagent recycling Optimization

"Construction Of A Diflunisal Ion Sensor And Its Use In Automated Flow Injection Methods For Assay, Content Uniformity And Dissolution Studies Of Formulations"
J. Pharm. Sci. 1995 Volume 84, Issue 7 Pages 889-894
Petr Solich, Michael A. Koupparis, Panos E. Macheras

Abstract: An ISE for diflunisal (I) of the PVC membrane-type was constructed by trapping the 0.01 M tetraheptylammonium-I liquid ion exchanger in 2-nitrophenyl octyl ether solution in a PVC matrix by the method of Craggs et al. (J. Chem. Educ., 1974, 51, 541). The electroactive membrane (diameter 6 mm) was attached to a commercially available nitrate electrode, placed in a potentiometric flow-through cell with Ag/AgCl (4 M KCl) as reference electrode and transferred to the flow injection analyzer.. Portions (85 µL) of sample in 10 mM NaOH were injected into a carrier stream of 10 mM NaOH (2.6 ml/min), mixed with a flow of 0.05 M Tris buffer of pH 8 (1.4 ml/min) in a 50 cm mixing coil and detected by the potentiometric ISE. The electrode exhibited a Nernstian response over the range 0.1-5 mM I and the detection limit was 0.026 mM. The RSD (n = 10) was 0.38% at 1 mM I. Under optimized conditions, the operative life of the ISE was 3 months. A diflunisal ion selective electrode of the PVC membrane type with an ion-exchanger consisting of the tetraheptylammonium-diflunisal ion pair is described. The sensor exhibits a rapid, near-Nernstian, selective response to diflunisal anion in the pH range 7-10, with a (batch) detection limit of 1 x 10^-5 M. The ion sensor was used as a flow detector in an automated flow injection analyzer to develop routine methods for assays (concentration range 1-50 x 10^-4 M, (flow) detection limit 2.6 x 10^-5 M), content uniformity, and dissolution studies of diflunisal formulations. No serious interference from common ions and tablet excipients was found, and the drug can be directly determined in colored samples without separation steps. Fourty measurements can be performed automatically per hour with a precision of 0.5-1.8% relative standard deviation. The automated method for the dissolution test provides a complete dissolution profile by the end of the experiment. Using the constructed ion sensor, the intramolecular hydrogen bonding of the diflunisal anion was studied, thereby revealing a new application of ion sensor potentiometry.
Diflunisal Electrode Potentiometry Electrode Sensor Interferences Dissolution rate Automation

"FIA Liquid-liquid Extraction Spectrophotometric Determination Of Phenothiazine Derivatives In Pharmaceuticals"
Lab. Rob. Autom. 1996 Volume 8, Issue 4 Pages 213-219
Petr Rychlovsk&yacute;*, Irena Nemcov&aacute;, Hana M&iacute;sarov&aacute;, Martina Zan&aacute;tov&aacute;

Abstract: Ground tablets were dissolved in water, filtered and portions (1 ml) of the resulting solution were injected into a stream (1 ml/min) of Britton-Robinson buffer of pH 3.4, which merged with a stream (0.2 ml/min) of 80 µM-Chromazurol S (Merck), then with a CHCl3 stream (0.7 ml/min) in a segmentor (0.4 mm i.d.) and passed through a PTFE extraction coil (160 cm x 0.5 mm i.d.). The flow then passed through a phase separator with a PTFE membrane. The organic phase (0.35 ml/min) passed through a 30 µL flow cell where chlorpromazine (I), diethazine (II) and fluphenazine (III) were detected at 503, 505 and 497 nm, respectively. Calibration graphs were linear up to 10.7, 10.1 and 15.3 µg/ml I, II and III, respectively, and the corresponding detection limits were 0.11, 0.04 and 0.13 µg/ml. The RSD (n = 10) at 8 µg/ml were 1.7-2.3% for the three analytes. Recoveries are not given. Determinations in tablets gave identical results to those obtained by a Czech standard method. The sample throughput was 15/h. The proposed extraction spectrophotometric determination of phenothiazine derivatives is based on the formation of ion associates of these derivatives with chromazurol S. The determination is carried out by flow-injection analysis (FIA). Teflon separators constructed in the laboratory were tested. Three derivatives of phenothiazine; chlorpromazine, diethazine, and fluphenazine were analyzed as the substances and in pharmaceutical form. The method provides correct and reproducible results. A very low detection limit and determination limit were attained (for diethazine, e.g., 0.04 g mL-1 and 0.14 g mL-1), so that the proposed method could also be used for monitoring small pharmaceutical concentrations. The frequency of analysis is 15 samples per hour.
Chlorpromazine Spectrophotometry Sample preparation Standard method Method comparison Teflon membrane Extraction Organic phase detection Phase separator

"Flow Injection Spectrophotometric Determination Of Hyrcanoside In Tablets"
Pharmazie 1993 Volume 48, Issue 3 Pages 194-196
Solich, P.;Karlicek, R.;Opletal, L.

Abstract: A flow-injection spectrophotometric determination of hyrcanoside based on the well-known reaction with picric acid in alkaline media using spectrophotometric detection at 486 nm is described. The calibration graph is rectilinear from 10^-400 mg L-1 hyrcanoside with a relative standard deviation of 1.6% for the 10 injections. The sampling rate was about 60 h-1 and the overall dispersion of the system was D = 5.7. This method was utilized for the content uniformity testing of experimental prepared tablets of hyrcanoside. (SFS)
Hyrcanoside Spectrophotometry

"Continuous Liquid-liquid Extraction Spectrophotometric Determination Of Diflunisal"
Pharmazie 1996 Volume 51, Issue 8 Pages 550-553
Trskova, R.;Rychlovsky, P.;Nemcova, I.;Turek, P.

Abstract: In the illustrated liquid-liquid extraction flow injection system, a stream of diflunisal (I) standard solution (0.8 mL/min) was merged with an air-segmented flow of Britton-Robinson buffer of pH 11 (0.56 mL/min) in a glass coil (35 cm x 1 mm i.d.). The merged solution was mixed with aqueous 0.5 mM methylene blue in a glass coil (35 cm x 1 mm i.d.). This solution was extracted with a stream of CHCl3 (0.7 mL/min) in a glass coil (100 cm x 1 mm i.d.) and the organic phase was separated and simultaneously deaerated prior to detection at 650 nm. Under optimum conditions, the calibration graph was linear from 0.025-5 µg/mL of I. RSD (n = 5) were 0.3-12.4% over the calibration range. The method was used to the analysis of I in ethanolic extracts of tablets. Results agreed with those of a control UV method.
Diflunisal Spectrophotometry Sample preparation Solvent extraction

"Flow Injection Spectrophotometric Determination Of Phenothiazines Using Analyte Oxidation In Manganese-dioxide-packed Reactors"
Pharmazie 1998 Volume 53, Issue 3 Pages 168-172
Pol&aacute;sek, M.; Dolejsov&aacute;, J.; Karlicek, R.

Abstract: A flow injection spectrophotometric method for determining 5 to 250 µg .cntdot. mL-1 of neuroleptic phenothiazines (namely prochlorperazine, thioridazine, levomepromazine, perphenazine, trifluoperazine and fluphenazine) using the analyte oxidation in manganese dioxide-packed reactors (50 mm x 1.2 mm) with aqueous 0.01 M sulfuric acid as carrier flow (0.6 mL .cntdot. min-1) has been devised. Active and stable reactor packings were prepared by coating sintered glass particles (diameter 0.4 to 0.5 mm) successively with an epoxide glue and powd. manganese dioxide or by thermal decomposition of Amberlite IRA-410 resin (20-50 mesh) in MnO4--form. At the injected sample volume of 100 pl the relative standard deviation was 1.2% (n = 10) when determining 75 µg .cntdot. mL-1 of prochlorperazine maleate in prepared solution of the pure substance and the sample throughput was 50 h-1. The method has been applied to the anal. of tablets and coated tablets containing prochlorperazine maleate, perphenazine, thioridazine hydrochloride or levomepromazine maleate. The results were in good agreement with those of the pharmacopoeial UV spectrophotometric determination.
Prochlorperazine Thioridazine Levomepromazine Perphenazine Trifluoperazine Fluphenazine Spectrophotometry Solid phase reagent Glass beads Amberlite Method comparison

"Flow Injection Analysis Of Ambroxol In Pharmaceutical Tablets"
Pharmazie 1998 Volume 53, Issue 3 Pages 203-204
Benli, P.; Tuncel, M.

Abstract: Flow injection analysis of ambroxol was investigated and optimized. Destilled water was a suitable solvent for ambroxol. Two maxima were observed by spectrophotometry in the spectrum of ambroxol at 209 and 244 nm. Well-shaped and nearly sym. peaks appeared employing an injection time of 2 s, keeping the absorbance at 209 nm, and a concentration. range between 1.03-5.15 x 10^-4 M. Reproducibility was 1.5% and a detection limit of 2.5 x 10^-5 M was calculated The method was applied to ambroxol tablets and the results were compared to those of UV-spectrophotometry. It is concluded that flow injection analysis is rapid, practical, accurate, and useful for routine anal. of ambroxol.
Ambroxol Spectrophotometry Method comparison Principal component analysis

"Flow Injection FTIR Determination Of Dimenhydrinate In Pharmaceuticals"
Quim. Anal. 1995 Volume 14, Issue 2 Pages 96-101
Bouhsain, Z.;Hasan, B.A.;Garrigues, S.;De La Guardia, M.

Abstract: Tablets, equivalent to 50 mg dimenhydrinate (I), were ground and homogenized and shaken in an ultrasound water bath with 10 mL CHCl3 or dichloromethane. The resulting solution was filtered and 300 µL of the filtrate was injected into a carrier stream (0.64 ml/min) of the dissolution solvent in the FIA manifold. The absorbance was measured by FTIR spectrometry at a maximum peak height at 1688 cm-1. The calibration graphs were linear up to 9.4 mg/ml of I in CHCl3 and CH2Cl2 with detection limits of 25 and 23 µg/ml, respectively. The RSD was 1.1% at 6 mg/ml in CHCl3 and 0.8% at 4 mg/ml in CH2Cl2. Results were compared to those obtained by batch analysis.
Drugs Dimenhydrinate Spectrophotometry Method comparison

"Acetaminophen Determination By Flow Injection Analysis With Biamperometric Detection"
Rev. Roum. Chim. 1998 Volume 43, Issue 9 Pages 811-816
Danet, A.F.;David, V.;David, I.

Abstract: A simple and rapid method was developed for the determination of acetaminophen using the analyte oxidation with Ce4+ in acidic medium and biamperometric detection of the Ce3+ formed. The measurements were performed with a dual channel flow injection system incorporating an amperometric detector with 2 Pt microelectrodes. The experimental parameters p.d. between microelectrodes, oxidant concentration. in the reagent stream, dispersion tubing length, total flow rate, and injected volume were optimized. Using an aqueous reagent stream containing 0.1 M Ce(SO4)2 in 1 M H2SO4 and 300 mV p.d., the detector response was linear up to 4 mM acetaminophen. The detection limit was 5 µM and 80 samples per h could be analyzed with a RSD of 1.8% at a 7 x 10^-4 M level (n = 10). The method was applied for acetaminophen determination in Paracetamol tablets. The results agreed well with data obtained by a reference method.
Drugs Acetaminophen Biamperometry Electrode Electrode Method comparison Optimization Kinetic

"Flow Injection Analysis Of Pharmaceutical Compounds. 4. Quantification Of Azintamide (Ora-gallin) In Tablets By UV-spectrophotometric Detection"
Sci. Pharm. 1987 Volume 55, Issue 4 Pages 259-265
Abdel Moety, E.M.;Moustafa, A.A.;Ahmad, A.S.K.;El Gendy, A.E.

Abstract: A solution of azintamide in ethanol is injected into a flow (2.2 mL min-1) of ethanol; the mixture passes through a mixing coil (30 cm), and the absorbance is measured at 258 nm. The calibration graph covers the range 5 (the limit of determination) to 50 µg mL-1. Recovery is quantitative. A sampling rate of 150 h-1 can be used. Results are compared with those of a static UV spectrophotometric method.
Azintamide Ora-gallin Electrode Spectrophotometry Method comparison Organic phase detection

"Determination Of Analgin By Flow Injection Analysis With Chemiluminescence Detection"
Shaanxi Shifan Daxue Xuebao (Ziran Kexue Ban) 1998 Volume 26, Issue 3 Pages 68-70
Li Liqing, Nie Feng, Yang Minli, Feng Manliang, Lu Jiuru

Abstract: A new method for the determination of analgin in tablets and injections by using flow injection chemiluminescence was based on the chemiluminescence reaction of analgin-KMnO4. The main factors which affect the determination were investigated. Under optimum conditions, the linear range for the determination of analgin was 1 x 10^-7-8 x 10^-5g/mL, the determination limit was 4.2 x 10^-8 g/mL.
Analgin Chemiluminescence Optimization

"Flow Injection With Online Dialysis-UV Spectrophotometric Determination Of Dissolution Of Paracetamol Tablets"
Shenyang Yaoke Daxue Xuebao 1998 Volume 15, Issue 1 Pages 62-64
Fang Qun, An Ziling, Fang Zhaolun, Zhang Shunli, Liu Zhisong, Sun Yuqing

Abstract: An automatic flow injection method for the dissolution test of drug preparations using the online dialysis was proposed. The dissolution of two paracetamol tablets was simultaneously monitored at 254 nm and 30 µL, and with monitoring rate 240 samples h-1. This method was particularly useful for monitoring fast dissolution processes.
Acetaminophen Spectrophotometry Dissolution rate Dialysis

"Determination Of Meprobamate By Using Modified Ammonium-selective Electrode-flow Injection Analysis Method"
Shenyang Yaoxueyuan Xuebao 1987 Volume 4, Issue 3 Pages 184-188
Li Chongjun Sun Jiakui

Abstract: The determination of meprobamate(I) in tablets is achieved by using an electrochemical flow injection system (flow diagram presented). A sample containing 200 mg of I was heated under reflux for 1 h with 70 mL of 6 M HCl. The hydrolysate was diluted to 250 mL with water and a portion (75 ml) of the solution was treated with 100 mL of water, adjusted to pH 6.5 with NaOH and diluted to 250 mL with water. A portion of sample solution (25 µL) was subjected to flow injection analysis and a modified NH3-sensitive electrode was developed to detect the NH3 produced by adding NaOH. Results agreed with those from the routine electrode method and the Chin. P. method (1985). The proposed method is rapid and accurate.
Meprobamate Electrode Method comparison

"Determination Of Rutin In Compound Rutin Tablets By Flow Injection Analysis"
Shenyang Yaoxueyuan Xuebao 1990 Volume 7, Issue 2 Pages 96-98
Gao Wenlan, Jia Ninghua, Sun Yuqing

Abstract: Powdered tablets, equivalent to 10 mg of rutin (I), were dissolved in 10 mL of 95% ethanol, diluted to 50 mL with water and the solution was filtered. After discarding the first few ml, portions (1 to 2 ml) of the filtrate were mixed with 3 mL of sodium acetate - acetic acid buffer solution (pH 6) and diluted to 10 mL with water. The content of I in the solution was determined by flow injection analysis with 50 mM AlCl3 as color reagent and detection at 420 nm. From 20 to 60 µg mL-1 of I could be determined. Mean recovery was 100.2% with a coefficient of variation (n = 8) of 0.5%.
Rutin Spectrophotometry

"Determination Of Amidopyrine In Qutong Tablets By Flow Injection Analysis"
Shenyang Yaoxueyuan Xuebao 1992 Volume 9, Issue 2 Pages 130-132
Du Kangping, Wang Yancong, Fang Zhaolun

Abstract: Powdered tablets (20 mg) are ultrasonically dissolved in and diluted to 100 mL with water. The supernatant is analyzed with an L2-1000 flow injection analyzer. (flow diagram given) for determination of amidopyrine (I) by reaction with 1% FeCl3 to form a blue-violet compound. The absorbance of the solution is measured at 556 nm vs. a water blank. Calibration graph is rectilinear for 10 to 90 µg mL-1 of I. For 10 to 30 µg mL-1 of I, recoveries range from 99.9 to 102.7% with coefficient of variation of 1.1%.
Amidopyrine Sample preparation Spectrophotometry

"Determination Of Paracetamol In Tablets By Flow Injection Analysis"
Shenyang Yaoxueyuan Xuebao 1993 Volume 10, Issue 1 Pages 60-62
Gao Wenlan Zhong Jide Dong Mingzhi

Abstract: The cited method is based on oxygenation of paracetamol (I) by ferriin under acidic conditions to form ferroin which is detected at 510 nm. The calibration graph was rectilinear from 180 to 540 µg mL-1 of I. Recoveries were 99.2 to 101% and coefficient of variation (n = 5) were 0.9%.
Acetaminophen Spectrophotometry

"FIA Method For Content Uniformity Examination Of Benzhexol Hydrochloride"
Shenyang Yaoxueyuan Xuebao 1994 Volume 11, Issue 2 Pages 108-111
Chen, Shujuan; Chen, Kejin; Zhang, Youqin; Li, Xiangdong; Xie, Guobin; Zhang, Zhengfu

Abstract: A flow injection analysis method with chloroform as the solvent for extraction has been developed for the examination of the content uniformity of benzhexol hydrochloride tablets. Optimum conditions were selected. The recovery was 98-101%. The calibration curve was linear in the range between 14.8-118.4 mmol/L. An examination rate of 60 samples/h was achieved with RSD 1.3%.
Drugs Benzhexol hydrochloride Dissolution rate Optimization

"Flow Injection Analysis Of Pharmaceutical Compounds. Determination Of Some Central Nervous System Acting Drugs By UV-spectrophotometric Detection"
Spectrosc. Lett. 1993 Volume 26, Issue 9 Pages 1649-1660
A. E. El-Gendy; M. G. El-Bardicyy; H. M. Loutfy; M. F. El-Tarras

Abstract: The Present work describes a direct flow injection analysis (FIA) of five commonly used central nervous system (CNS) acting drugs namely amitriptyline hydrochloride, carbamazepine, clomipramine hydrochloride, fluphenazine hydrochloride and imipramine hydrochlorode. The characteristics of the system and the conditions of the spectrophotometric determination are evaluated. The proposed technique can be applied for pharmaceutical quality control of the pure material and pharmaceutical dosage forms containing the drug. Amount ranging from 16 to 80 bµml-1 of amitriptyline hydrochloride, carbamazepine and fluphenazine hydrochloride and from 32 to 160 bµ mL-1 of clomipramine hydrochloride and imipramine hydrochloride dissolved and/or extracted in ethanol could be accurately analyzed. Standard addition (0.5 to 3 times of the claimed amounts) of authentic samples to powdered tablets gave good mean percent recoveries with low standard deviations. Samples can be introduced at rates of about 180 per hour or even more. The results obtained by applying the proposed FIA method are statistically analyzed and compared with those obtained from applying pharmacopoeial procedures.
Drugs Amitriptyline hydrochloride Carbamazepine Clomipramine hydrochloride Fluphenazine hydrochloride Imipramine hydrochloride Spectrophotometry Organic phase detection

"A Rapid FIA-spectrophotometric Method With Online Extraction For The Content Uniformity Test Of Atropine Sulfate Tablets"
Yaoxue Xuebao 1990 Volume 25, Issue 3 Pages 198-203
Qu XY, He CF, Sun LJ, Wang X, Luo X

Abstract: A rapid spectrophotometric method based on FIA for the content uniformity test of atropine sulfate tablets has been developed. By means of the self-designed FIA system with an online extraction device, many difficulties resulting from extraction, such as slow analytical rate, environmental pollution, poor reproducibility, etc, were overcome, and the routine procedure of the official content uniformity test was tremendously simplified. Results obtained with the proposed method agree well with those obtained with the official test. Furthermore, the proposed method attained a sampling rate of 60 samples per hour, a recovery of 100.0%, a relative standard deviation of 0.7%, and a detection limit of 0.24 µg/ml. Uniform design proves effective to optimize complex FIA conditions, and FIA promises a new approach to test the content uniformity of pharmaceutical tablets.
Atropine sulfate Spectrophotometry Sample preparation Extraction Method comparison Optimization

"Solvent Extraction-flow Injection Analysis For Determination Of Trimethoprim In Compound Preparations"
Yaoxue Xuebao 1991 Volume 26, Issue 9 Pages 710-713
Liu WZ, Gao JQ

Abstract: Trimethoprim (TMP) in four pharmaceutical preparations (compound sulfamethoxazol tablets, compound tetracycline tablets, compound trimethoprim and sulfamethoxazol tablets; and compound berberine injection) is determined by solvent extraction-flow injection spectrophotometry. It can be extracted into chloroform directly, and the absorbance at a wavelength of 280 nm of the organic phase is measured after phase separation. The manifold comprises two streams. The sample is injected into a 0.2 mol/L NaOH carrier stream, and extracted with chloroform in a 200-cm coil (ID 0.7 mm) after a 50 cm reaction tube (ID 1.0 mm). Calibration graph is linear in the range of 25-150 µg/ml. The average recovery is 101.4% with a relative standard deviation of 1.1%. The proposed system permits the analysis of about 50 samples per hour. Precise results in agreement with those obtained with official methods are achieved. Trimethoprim (I) in four pharmaceutical preparations, viz., (i) compound sulfamethoxazol (II) tablets, (ii) compound tetracycline tablets, (iii) compound I and II tablets, and (iv) compound berberine injection, was determined by the cited method. The solvent extraction - flow injection spectrophotometric system and its principle were described and illustrated. The sample was injected into a carrier stream of 0.2 M NaOH and extracted with CHCl3 on a coil (200 cm x 0.7 mm), and then passed through a reaction tube (50 cm x 1 mm). The absorbance of I in CHCl3 phase was measured at 280 nm. Calibration graph was rectilinear for 25 to 150 µg mL-1 of I. The mean recovery was 101.4%, with coefficient of variation (n = 4) of 1.1%. Results agreed with those obtained by the official methods.
Trimethoprim Spectrophotometry Sample preparation Phase separator Solvent extraction

"Preparation Of Tubular Flow-through Atropinium Sensor And Its Application In A Flow Injection System"
Yaowu Fenxi Zazhi 1989 Volume 9, Issue 6 Pages 347-350
Cui, H.B.;Sun, J.Y.;Li, B.;Zhang, Z.;Fang, Y.

Abstract: The cited ion-selective electrode is prepared by applying a solution containing 1% of atropine - tetraphenylboric acid ion associate, 68% of dibutyl phthalate and 31% of PVC powder in THF to a PVC tube (35 mm x 1 mm) with a 1.5-mm hole in the middle (diagram given). To determine atropine sulfate (I), ground tablets (300 mg) are mixed with 0.1 M Mg acetate to 50 ml, the solution is filtered and a 1 mL portion is further diluted with 0.1 M Mg acetate to a known volume A 300 µL aliquot of the solution is carried by a 0.1 M Mg acetate stream to the electrode in a flow injection analyzer.. Recovery was 98 to 101% and the coefficient of variation was 1.2%. Results agreed closely with those of the Chin. P. The electrode has a life-span of over 1 year.
Atropine sulfate Electrode Electrode Sensor Method comparison

"Determination Of Clonidine In Its Preparations By Solvent Extraction - Flow Injection Analysis"
Yaowu Fenxi Zazhi 1992 Volume 12, Issue 3 Pages 135-138
Liu, W.Z.;Chen, H.

Abstract: A sample of clonidine hydrochloride (I) tablets (equivalent to ~0.5 mg of I) was dissolved in and diluted with Na2HPO4 - citric acid buffer (pH 4) to 100 mL. After centrifugation, 150 µL of the solution was injected into the flow injection apparatus (diagram illustrated) with water as carrier (2 mL min-1) then reacted with a reagent stream of bromophenol blue in the above buffer (2 mL min-1). The resulting ion associate flows to the extraction tube (2.5 m x 0.7 mm), is extracted with CHCl3 (2.5 mL min-1) and I is detected at 413 nm. The calibration graph was rectilinear for 15 to 70 µg mL-1 of I, the detection limit was 0.2 µg mL-1 and the coefficient of variation was 0.85%. Average recovery was 100.4%.
Clonidine Spectrophotometry Sample preparation Ion pair extraction Organic phase detection Solvent extraction

"Flow Injection Spectrophotometric Method For The Determination Of Vitamin B6"
Yaowu Fenxi Zazhi 1994 Volume 14, Issue 3 Pages 14-16
Liu Wanzhong, Wang Chaodong, Chen Hao

Abstract: Sample was dissolved in 50% ethanol to a concentration of 30 µg/ml of vitamin B6 (I) and then 200 µL of the solution was injected into the FIA system and carried at 1.5 ml/min by a stream of 50% ethanol to mix with streams of 20% sodium acetate and 0.5% chloroimino-2,6-dichloroquinone in 50% ethanol in a reaction tube (400 cm x 0.8 mm i.d.) before detection at 650 nm. Calibration graphs were linear for 3-60 µg/ml of I. Only tetracyclines and phenols interfered. Recovery was 99.7% with RSD of 0.8%. The method was applied to the assay of single- and compound-formulated I tablets. The sampling frequency was 150 runs per h.
Vitamin B6 Spectrophotometry Interferences

"Flow Injection Determination Of Prednisone Acetate"
Yaowu Fenxi Zazhi 1998 Volume 18, Issue 3 Pages 168-170
Liang Yaodong,Li Jianzhong and Zhang Zhujun, Zhang Xiaoqing

Abstract: Based on the enhancement of chemiluminescence reaction of prednisone acetate on the cerium IV and sulfite system, a flow injection chemiluminescence method was developed for determination of prednisone acetate. Linear range was 0.2-20.0 mg/L, detection limit was 0.031 mg/L, and RSD was 1.8 in 11 parallel determinations in the sample concentration. of 0.2 mg/L. The method was used in determination of prednisone acetate in tablets with good results.
Prednisone acetate Chemiluminescence Indirect

"Study On Chemiluminescence System Of Potassium Permanganate/levodopa In Assay Of Levodopa"
Yaowu Fenxi Zazhi 1998 Volume 18, Issue 1 Pages 41-45
Yang Minli, Li Liqing, Feng Manliang and Lu Jiuru

Abstract: A sample solution was diluted with water to 25 mL and then analyzed by FIA (diagram given). The sample mixed with streams of 0.05 M KMnO4 and 1 M H6P4O13 in the flow injection system and the chemiluminescence thus generated was measured. The calibration graph for levodopa (dopa) was linear from 0.4-80 mg/l and the detection limit was 62 g/l. The method was also used to analyze tablets; RSD were 1.6%. The results were compared with those obtained by UV spectrophotometry. None of the investigated co-existing components interfered. The FIA sample throughput was 120/h. In this paper,a new chemiluminescence system of potassium permanganate-levodopa was investigated and a new chemiluminescence method for the determination of levodopa with flow injection technique was established. The concentration range of linear response is 4 x 10^-4~8 x 10^-2g/L.The detection limit is 6.2 x 10^-5g/L with a relative standard deviation of 1.6% for the determination of 4 x 10^-3g/L of levodopa(n=11). The method has been used to determine the content of levodopa in tablets with satisfactory results.
Levodopa Chemiluminescence Interferences

"Construction And Application Of All-solid-state Aconitine Electrochemical Detector In Flow Injection Analysis"
Yaoxue Xuebao 1992 Volume 27, Issue 4 Pages 294-298
Liu WZ, Zuo AL

Abstract: The cited detector exhibits Nernstian response for aconite (I) and its derivatives, with a slope of 56 mV per decade from 30 µM to 30 mM at pH 2 to 7. Direct potentiometry for I in Aconitum kusnezoffi and A. carmichaeli showed recoveries of 96.8 to 98.5%, with coefficient of variation of 1.8 to 3.5%. The detector can be applied to determine I and its derivatives in samples by flow injection analysis. An all-solid-state electrochemical detector used in flow injection analysis for determining aconitine (I), mesaconitine (II) and hypaconitine (III) was constructed (diagram given). For determination of the aconitines in Aconitum kusnezoffii Reichb, Aconitum carmichaeli Debx. and xiaohuoluo pills, sample (10 g) was extracted with 50 mL of 7 M NH3 and 100 mL of ethyl ether, the ether layer was evaporated to dryness and the residue was dissolved in 5 mL each of 0.1 M HCl and 1 M phosphate buffer solution (pH 6.5) and water to 50 mL. A 400 µL portion of the solution was injected into the flow system. Nernstian response was observed for 10 mM to 30 µM I, II or III and the electrode was stable for 6 h. The mean recoveries of I to III were 98.5, 98.3 and 96.8%, respectively; corresponding coefficient of variation were 1.8, 2.4 and 3.5%. Results agreed with those obtained by spectrophotometry (Ch. P. 1990). A new kind of all-solid-state electrochemical detector for very toxic alkaloids such as aconitine, mesaconitine and hypaconitine was studied. It exhibits Nernstian response for these alkaloids with a slope of 56 mV/decade over the concentration range of 3 x 10^-5 to 1 x 10^-2 mol/L at pH 2-7 under the flow condition. Direct potentiometry for the determination of aconitine in Aconitum kusnezoffii Reichb., Aconitum carmichaeli Debx. and Xiaohuoluowan showed average recoveries of 98.5, 98.3 and 96.8% and relative standard deviations of 1.8, 2.4 and 3.5%, respectively. It can be used for the determination of very toxic alkaloids in the above mentioned samples by flow injection analysis It also can be used for the study of the hydrolytic kinetics of aconitine.
Aconitine Mesaconitine Hypaconitine Potentiometry Kinetic Method comparison

"Flow Injection Analysis For The Content Test Of Codeine Phosphate Tablets"
Yaoxue Xuebao 1994 Volume 29, Issue 12 Pages 905-909
Fang, Q.; Luo, X. (SFS)

Abstract: A new flow injection system using UV detector and adopting an on-line adsorption column to eliminate the interference of excipients is proposed for the content uniformity test of codeine phosphate tablets. The results obtained with this system agree well with those by the conventional method. The proposed system with a sample volume of 60 µL, sampling frequency of 60/h and precision of 0.8% (RSD, n = 40) is suitable for the content uniformity test and assay of codeine tablets as well as those of other dosage forms.
Codeine phosphate Spectrophotometry Interferences Method comparison Column

"Determination Of Trace Arsenic In Spirulina Plaensis Tablets By Flow Injection Hydride Generation Atomic Fluorescence Spectrometry"
Zhongguo Yaoke Daxue Xuebao 1998 Volume 29, Issue 6 Pages 473-474
Dong Shunling

Abstract: A method for determination of trace arsenic in Spirulina plaensis tablets by flow injection hydride generation atomic fluorescence spectrometry was developed. Digesting sample with HNO3-H2SO4-HCIO4 (20: 1: 1) mixed acid, and potassium iodide and ascorbic acid were chosen as the interference suppressing agents. The characteristic concentration. (0.0044 absorption) was 0.2 ng/ ml, the average recovery was 96 .6% (n=5, RSD=2. 8%), within 1. 0~5. 0 ng/ ml, arsenic had a good linearity, and the least square equation is y=0.205x-0. 0001 (r=0. 9994, n=5).
Arsenic Fluorescence Interferences

"Flow Injection Analysis Of Tablets And Injection Of Ascorbic Acid"
Zhongguo Yiyao Gongye Zazhi 1995 Volume 26, Issue 2 Pages 70-72
NAHE Hua;SHEN You-Chang;QI Xue-Yong;NI Qun-Yi;JIANG Ying

Abstract: Ascorbic acid was determined by FIA based on the formation of ferroin when ascorbic acid reacted with a mixture of iron (III) and 1,10-phenanthroline and measurement of the absorbance at 510 nm. This simple and rapid method gave the comparable results of the official method.
Ascorbic acid Spectrophotometry Indirect Method comparison Standard method

"Determination Of Dissolution Rate Of Zinc Gluconate Tablets By FIA-spectrophotometry"
Zhongguo Yiyao Gongye Zazhi 1996 Volume 27, Issue 8 Pages 365-367
ZHANG Jie-Bin;ZHOU Guo-Hua

Abstract: The experimental conditions for determination of dissolution rate of zinc gluconate were studied by flow injection analysis. The dissolution rate of zinc gluconate tablets from different pharmaceutical factories was determined by the method. The mean recovery was 99.7+-0.78%, RSD=0.32%.
Zinc gluconate Spectrophotometry Dissolution rate Optimization

"Determination Of Potassium Iodide Sugary Pills By FIA Spectrophotometry"
Zhongguo Yiyao Gongye Zazhi 1998 Volume 29, Issue 10 Pages 32-34
MA Yong*, TONG De-Yong, SHAO Hong

Abstract: A rapid spectrophotometric method of flow injection analysis (FIA) has been developed for the determination of potassium iodide sugary pills. It is based on the catalytic effect of I- in the reaction of Ce4+-As3+. The I- concentration. range of determination is 0-5.0 µg/mL.
Iodide Spectrophotometry Catalysis Indirect

"Dissolution Profiles Of Chloroquine Tablets Using A Flow-through Chloroquine Sensor"
IEEE Proc. 2005 Volume SPBR, Issue 1 Pages 22-25
Zain, Z.M. Saad, B. Rahman, I.Ab. Mahsufi, S.

Abstract: A potentiometric polyvinyl chloride membrane comprising of bis(2-ethylhexyl)adipate as plasticizer and potassium tetrakis(4-chlorophenyl)borate was developed as a chloroquine sensor. The sensor was later applied as a detector in a flow injection analysis set up where it was not only successfully used in the determination of active ingredient in pharmaceutical preparations but also in establishing the dissolution profiles for chloroquine tablets. The flow through chloroquine sensor offers high accuracy and excellent repeatability, with large sample throughput (90 mL min-1). Besides being simple, the technique is rapid, low cost and allows direct quantification of chloroquine (without sample pretreatment).
Chloroquine Sensor Potentiometry Electrode Dissolution rate

"Determination Of Leflunomide In Pharmaceutical Tablets By Flow-Injection Analysis"
J. Liq. Chromatogr. Relat. Technol. 2005 Volume 28, Issue 11 Pages 1693-1701
Duygu Yeniceli, Dilek Dogrukol-Ak, Muzaffer Tuncel

Abstract: A flow injection analysis (FIA) of leflunomide using UV-detection is described, in this study. The most suitable carrier solvent was found to be an aqueous solution of ethanol (25%, v/v). Leflunomide was determined at the optimum conditions, such as flow rate of 0.8 mL min-1 and detection wavelength of 260 nm. The method has been validated and linearity was examined in the range of 2.75 x 10^-6-1.10 x 10^-4 M. The limit of detection (LOD) and quantitation (LOQ) were calculated to be 2.60 x 10^-7 M (S/N=3.3) and 7.87 x 10^-7 M (S/N=10), respectively. The application of the proposed method has been performed in pharmaceutical tablets of leflunomide and excellent results were obtained. The results were compared with those obtained from UV-spectrophotometry. Insignificant difference was found between the methods. As a result, the FIA method for the determination of leflunomide in pharmaceutical tablets can be proposed as a precise, accurate, sensitive, and cheap method for routine analysis laboratories.
Leflunomide Spectrophotometry Method comparison Optimization

"Simultaneous Determination Of Rifampicin And Isoniazid By Continuous-flow Chemiluminescence With Artificial Neural Network Calibration"
Anal. Bioanal. Chem. 2005 Volume 383, Issue 5 Pages 817-824
Baoxin Li, Yuezhen He, Jiagen Lv and Zhujun Zhang

Abstract: In this paper a continuous-flow chemiluminescence (CL) system with artificial neural network calibration is proposed for simultaneous determination of rifampicin and isoniazid. This method is based on the different kinetic spectra of the analytes in their CL reaction with alkaline N-bromosuccinimide as oxidant. The CL intensity was measured and recorded every second from 1 to 300 s. The data obtained were processed chemometrically by use of an artificial neural network. The experimental calibration set was 20 sample solutions. The relative standard errors of prediction for both analytes were approximately 5%. The proposed method was successfully applied to the simultaneous determination of rifampicin and isoniazid in a combined pharmaceutical formulation.
Isoniazid Rifampicin Chemiluminescence Calibration Neural network

"Validated Method For The Determination Of Deflazacort By A Flow-Injection Analysis With UV Detection: Application To Pharmaceutical Formulations"
J. Liq. Chromatogr. Relat. Technol. 2004 Volume 27, Issue 16 Pages 2593-2601
Derya Yapar, Ar&#05;n G&uuml;l Dal, Muzaffer Tuncel, &Uuml;lk&uuml; Dilek Uysal

Abstract: A simple, precise, accurate, and fast flow-injection analysis (FIA) method employing UV detection is described for the determination of deflazacort (DEF) in pharmaceutical tablets. The best carrier solvent system consisted of EtOH: sodium dihydrogen phosphate (0.2 M) (20:80, v/v) (pH 6.0). Related parameters were elucidated and a flow-rate of 1.3 mL min-1 was used and the analyte was monitored at 247 nm. In the optimum condition, the repeatability was in the range of 0.27-0.41 as intra-day precision. The linearization was tested considering intra- and inter-day experiments in the range of 1.0 x 10^-5 - 5.0 x 10^-5 M and good correlation coefficients were obtained. The limit of detection (LOD) and the limit of quantification (LOQ) were calculated to be 2.35 x 10^-7 and 7.04 x 10^-7 M, respectively, as inter-day results. The proposed method was applied to the determination of DEF in pharmaceutical preparations. Conventional UV-spectrophotometry was used as a comparison method and their results were also compared to those of the FIA technique. Insignificant differences between FIA and UV-spectrophotometric results were observed (p< 0.05). In conclusion, the tablets provide the general official requirements, 101.3% and 102.3%, respectively. Therefore, the proposed method is suggested to the routine laboratories for the determination of DEF in tablets.
Deflazacort Spectrophotometry Method comparison Standard method Optimization

"Rapid Determination Of Naproxen Sodium In Pharmaceutical Formulations By Flow Injection Analysis (FIA) Using UV-Detection"
J. Liq. Chromatogr. Relat. Technol. 2003 Volume 26, Issue 3 Pages 401-408
Erol Sener, Muzaffer Tuncel, Hassan Y. Aboul-Enein

Abstract: A flow injection analysis (FIA) of Naproxen sodium (NAPS) using UV detection is described in this study. The best solvent system used as a carrier solution was found to be an aqueous solution of EtOH (10% v/v). A flow-rate of 1.2 mL min-1 was used and Naproxen was detected at 230 nm. Repeatability was examined using 8 x 10^-6 M NAPS solution and relative standard deviation (RSD) values were found to be about 2.2 for intra-day and inter-day studies. The calibration equation was the linear range of 4 x 10^-6 to 1.18 x 10^-5 M. Limit of detection (LOD) and limit of quantification (LOQ) were calculated as 5.8 x 10^-7 (S/N=3.3) and 1.7 x 10^-6 M (S/N=10), respectively. The proposed method was applied for the determination of NAPS in pharmaceutical tablet formulation, containing 275 mg active material. The proposed method is reliable, precise, accurate, and rather cost effective, and can be applied for uniformity tests in NAPS tablets.
Naproxen Spectrophotometry Optimization

"Separation And Determination Of Sulfonamides In Pharmaceutical Preparations By A Microfluidic Capillary Electrophoresis System With A Continuous Sample Introduction Interface"
J. Sep. Sci. 2003 Volume 26, Issue 15-16 Pages 1376-1382
Liu Yin Fan, Hong Li Chen, Xing Guo Chen *, Zhi De Hu

Abstract: A simple, rapid microfluidic capillary electrophoresis system with a continuous sample introduction interface is described in the present paper. The interface with an H-channel structure was produced using a non-lithographic approach. The H-channel structure fixed on a planar plastic base utilized a horizontal 6.5-centimeter-long separation capillary with two vertical sidearm tubes on each end that served as inlet and outlet flow-through electrode reservoirs. The inlet reservoir also functioned as interface for coupling to the FI system. The performance of the system was demonstrated in the separation and determination of trimethoprim (TMP), sulfadiazine (SDZ), and sulfamethoxazole (SMZ) with UV detection at 214 nm, achieving baseline separation within 2.5 min. The sample throughput rate can reach up to 30 samples h-1. The repeatability (defined as relative standard deviation, RSD) was 2.23%, 1.19%, 2.64% with peak height evaluation and 2.43%, 1.46%, 3.58% for peak area evaluation, respectively. The limits of detection (S/N = 3) were 0.17 g/mL, 1.05 g/mL, and 1.28 g/mL for TMP, SDZ, and SMZ, respectively. This technique has been applied to the analysis of two commercial pharmaceutical preparations containing TMP, SDZ, and SMZ for the first time and has achieved satisfactory results.
Sulfoamides Trimethoprim Sulfadiazine Sulfamethoxazole Spectrophotometry Electrophoresis Interface

"Flow Injection Analysis NMR (FIA-NMR): A Novel Flow NMR Technique That Complements LC-NMR And Direct Injection NMR (DI-NMR)"
Magn. Reson. Chem. 2003 Volume 41, Issue 7 Pages 509-516
Paul A. Keifer

Abstract: Details of a new flow NMR technique, flow injection analysis NMR (FIA-NMR), are presented for the first time. This method blends some aspects of both liquid chromatography-NMR and direct injection NMR, and complements both. FIA-NMR is shown to be useful as an analytical technique, especially for repetitive analyzes, and may also prove useful in the analysis of combinatorial chemistry libraries. The feasibility of FIA-NMR is demonstrated by the quantitative analysis of an over-the-counter pharmaceutical.
Caffeine Nuclear magnetic resonance Interface

"A Simple Solid Phase Spectrofluorimetric Method Combined With Flow Analysis For The Rapid Determination Of Salicylamide And Salicylic Acid In Pharmaceutical Samples"
Fresenius J. Anal. Chem. 1999 Volume 365, Issue 7 Pages 619-624
A. Ruiz Medina, M. L. Fern&aacute;ndez de C&oacute;rdova, A. Molina D&iacute;az

Abstract: A new, sensitive and very simple spectrofluorimetric biparameter sensor is described for the determination of salicylamide and/or salicylic acid in pharmaceutical preparations. The method integrates the transitory retention and fluorescence detection of both compounds on Sephadex QAE A-25 resin packed into a conventional flow-through cell. A monochannel manifold with two alternative carriers is used. At pH 2.0 (first carrier) salicylic acid is selectively retained on the solid support and after developing the analytical signal it is desorbed. At pH 11.0 (second carrier) both salicylic acid and salicylamide are simultaneously and transitorily retained on the solid, the analytical signal now corresponding to both analytes. The monochromators were tuned at 260 (excitation) and 415 (emission) nm, respectively. The calibration graph for salicylamide is linear over the range 0.01 to 0.32 wg mL-1 and for salicylic acid from 0.04 to 1.0 wg mL-1 in the presence of each other. The relative standard deviation and the sampling frequency for the determination of salicylamide (0.20 wg mL-1) and salicylic acid (0.50 wg mL-1) were 1.1% and 35 h-1, and 0.9% and 45 h-1, respectively. Good results on application to individual determination or mixture resolution in pharmaceutical samples testify to the usefulness of the proposed sensor.
Salicylic acid Salicylamide Fluorescence Method comparison Optimization Sephadex Resin Solid phase extraction

"Simultaneous Determination Of Paracetamol And Caffeine By Flow Injection-Solid Phase Spectrometry Using C18 Silica Gel As A Sensing Support"
Anal. Sci. 2002 Volume 18, Issue 11 Pages 1241-1246
P. Ortega-barrales, R. Padilla-weigand And A. Molina-d&iacute;az

Abstract: A continuous and simple UV-photometric flow-through biparameter-sensing device has been developed for the simultaneous determination of paracetamol and caffeine at 275 nm. The sensor is based on temporary sequentiation in the arrival of the analytes to the sensing zone by on-line separation using C18 bonded phase beads (the same as that used in the sensing zone) placed into a minicolumn just before the flow cell. The sample containing these compounds is injected into the carrier solution; paracetamol is determined first because it passes through the minicolumn, while caffeine is strongly retained in it. Then, caffeine is conveniently eluted from the precolumn and develops its transitory signal. Using 200 µL of a sample and deionized water as a carrier, the analytical signal showed a very good linearity in the ranges of 10 - 160 µg mL-1 and 3.5 - 50 µg mL-1 with detection limits of 0.75 and 0.56 µg mL-1 for paracetamol and caffeine, respectively. If deionized water with the pH adjusted at 12 was used as a carrier solution, these parameters were 25 - 400 and 4 - 55 µg mL-1 with 2.0 and 0.50 µg mL-1 as the detection limits, respectively. The biparameter optosensor was satisfactorily applied to the simultaneous determination of these two analytes in pharmaceuticals.
Acetaminophen Caffeine Spectrophotometry Optimization Interferences