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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Rapid Communications in Mass Spectrometry

  • Publisher: Wiley
  • FAD Code: RCMS
  • CODEN: RCMSEF
  • ISSN: 0951-4198
  • Abbreviation: Rapid Commun. Mass Spectrom.
  • DOI Prefix: 10.1002/rcm
  • Language: English
  • Comments: Fulltext from 1987 V1

Citations 52

"Analysis Of Succinylacetone, As A Girard T Derivative, In Urine And Dried Bloodspots By Flow Injection Electrospray Ionization Tandem Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2007 Volume 21, Issue 1 Pages 59-63
David W. Johnson, Rosemarie Gerace, Enzo Ranieri, Minh-Uyen Trinh, Ralph Fingerhut

Abstract: Flow injection electrospray ionization tandem mass spectrometric methods for succinylacetone (SA) in 250 µL urine, using d5-SA as internal standard, and in 3 mm dried bloodspots, using 13C 4-SA as internal standard, are described. Selectivity and sensitivity of analysis is achieved by the use of a mono-Girard T derivative. Measured SA infant urine normal range (n = 20) is 0.013-0.27 µmol/mmol creatinine. Measured SA newborn bloodspot normal range (n = 152) is 0-0.30 ?mol/L. Bloodspots from children with hepatorenal tyrosinemia type 1, and kept at room temperature for up to 7 years, afforded SA concentrations of 0.9-5.7 µmol/L.

"Selectivity Of Electrospray Response In Small Polymer Analysis By Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2006 Volume 20, Issue 21 Pages 3188-3192
Salimo Mohamed, Laurence Charles

Abstract: The selectivity of electrospray was explored for a small poly(ethylene)glycol by comparing the oligomer response obtained from direct polymer introduction in flow injection analysis with the signal recorded in high-performance liquid chromatography/mass spectrometry (HPLC/MS). When the oligomer mixture was ionized, a suppression effect was measured for all but the more hydrophobic congeners for which the response was enhanced. This result would reflect the influence of electrospray droplet chemical composition on the equilibrium partitioning coefficient in Enke's model. On average, the electrospray selectivity observed for the studied poly(ethylene)glycol did not affect the molecular weight distribution parameters as response for the most concentrated oligomers was suppressed to the same extent while over-expressed largest congeners had a low contribution to the total polymer sample.

"Systematic Examination Of The Signal Area Precision Of A Single Quadrupole Enhanced Low Mass Option (ELMO) TSQ Mass Spectrometer"
Rapid Commun. Mass Spectrom. 2006 Volume 20, Issue 16 Pages 2419-2426
Klaus Fischer *, Susanne Höffler, Axel Meyer

Abstract: To examine the precision of the signal area response of an enhanced low mass option (ELMO) MSQ? mass spectrometer, operated in the negative electrospray ionization (ESI) mode, extended tests were performed, using flow injection analysis mass spectrometry (FIA-MS). Analytes were nitrate, nitrite, malonic acid, and D,L-mandelic acid. Composition and concentration of injected samples, application of an ASRS anion suppressor and of the cone wash unit, methanol addition to the FIA flow medium, and the voltage bias of the hexapole transfer lens were test variables. Individual test cycles comprised up to 90 injections, processed within 20 h. With a few exceptions the signal response tended to decline over time leading to a loss of more than 80% of the initial signal area in extreme cases. A hexapole radiofrequency (RF) voltage bias of -0.3 V led to an overall low detector response and to high losses of sensitivity over time. Other correlations between the insufficient signal reproducibility and FIA-MS operating conditions could not be established. The test scheme gave hints how to localize the cause of the mass spectrometer malfunction. The repetition of the test scheme after remedying the detected electronic default demonstrated that relative standard deviations less than 5% can be achieved for a sequence of 30 injections if methanol is added to the FIA flow medium and if a suppressor is used. Based on these findings a recommendation is formulated to supplement current test schemes for instrument performance verification by a detector response precision criterion.

"Comparison Of Flow Injection Analysis Electrospray Mass Spectrometry And Tandem Mass Spectrometry And Electrospray High-field Asymmetric Waveform Ion Mobility Mass Spectrometry And Tandem Mass Spectrometry For The Determination Of Underivatized Amino Acid"
Rapid Commun. Mass Spectrom. 2006 Volume 20, Issue 11 Pages 1801-1808
Margaret McCooeye, Zoltán Mester

Abstract: Twenty proteinogenic amino acids (AAs) were determined without derivatization using flow injection analysis followed by electrospray ionization mass spectrometry and tandem mass spectrometry (ESI-MS and ESI-MS/MS) and electrospray ionization high-field asymmetric waveform ion mobility mass spectrometry and tandem mass spectrometry (ESI-FAIMS-MS and ESI-FAIMS-MS/ MS), in positive and negative ionization modes. Three separate sets of ESI-FAIMS conditions were used for the separation and detection of the 20 AAs. Typically ESI-FAIMS-MS showed somewhat improved sensitivity and significantly better signal-to-noise ratios than ESI-MS mainly due to the elimination of background noise. However, the difference between ESI-FAIMS-MS and ESI-MS/MS was significantly less. ESI-FAIMS was able to partially or completely resolve all the isobaric amino acid overlaps such as leucine, isoleucine and hydroxyproline or lysine and glutamine. Detection limits for the amino acids in ESI-FAIMS-MS mode ranged from 2 ng/mL for proline to 200 ng/mL for aspartic acid. Overall, ESI-FAIMS-MS is the preferred method for the quantitative analysis of AAs in a hydrolyzed yeast matrix.

"Use Of Flow Injection Atmospheric Pressure Photoionization Quadrupole Time-of-flight Mass Spectrometry For Fast Olive Oil Fingerprinting"
Rapid Commun. Mass Spectrom. 2006 Volume 20, Issue 8 Pages 1181-1186
J. L. Gómez-Ariza*, A. Arias-Borrego, T. García-Barrera

Abstract: The recently introduced technique of an atmospheric pressure photoionization (APPI) source coupled to quadrupole time-of-flight mass spectrometry (QqTOFMS) has been applied to fast olive oil fingerprinting on the basis of the accurate mass measurements obtained with this instrumentation. The key compounds can be characterized as [M+H]+ (produced by proton transfer) or as [M]+. (by charge transfer) ions in the mass spectra. [M+H]+ ions, however, show higher abundance, especially for triacylglycerols. Other ions present in APPI-MS are the acylium ion [RiCO]+ and [RiCOH2O]+. This latter ion is absent in the electrospray ionization (ESI)-MS spectra, and this represents valuable complementary information. Several critical parameters in the APPI source were optimized such as LC eluent composition, ion spray voltage and, especially, declustering potential. APPI-QqTOFMS allows easy discrimination among different edible oils: olive, extra virgin olive, olive-pomace, hazelnut, sunflower, corn and several mixed oils, with high throughput (approximately 1 min per sample). Cluster analysis was applied to obtain the best experimental conditions for oil discrimination on the basis of declustering potential. Principal components analyzes of these APPI-MS spectra show that the approach can be used for studies of olive oil adulteration with other oils, even in the case of hazelnut oil that exhibits a high chemical similarity with olive oil.

"Isotope Ratio Monitoring Of Small Molecules And Macromolecules By Liquid Chromatography Coupled To Isotope Ratio Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2005 Volume 19, Issue 18 Pages 2689-2698
Jean-Philippe Godin, Jörg Hau*, Laurent-Bernard Fay, Gérard Hopfgartner

Abstract: In the field of isotope ratio mass spectrometry, the introduction of an interface allowing the connection of liquid chromatography (LC) and isotope ratio mass spectrometry (IRMS) has opened a range of new perspectives. The LC interface is based on a chemical oxidation, producing CO2 from organic molecules. While first results were obtained from the analysis of low molecular weight compounds, the application of compound-specific isotope analysis by irm-LC/MS to other molecules, in particular biomolecules, is presented here. The influence of the LC flow rate on the CO2 signal and on the observed 13C values is demonstrated. The limits of quantification for angiotensin III and for leucine were 100 and 38 pmol, respectively, with a standard deviation of the 13C values better than 0.4. Also, accuracy and precision of 13C values for elemental analyzer.-IRMS and flow injection analysis-IRMS (FIA-LC/MS) were compared. For compounds with molecular weights ranging from 131 to 66 390 Da, precision was better than 0.3, and accuracy varied from 0.1 to 0.7. In a second part of the work, a two-dimensional (2D)-LC method for the separation of 15 underivatised amino acids is demonstrated; the precision of 13C values for several amino acids by irm-LC/MS was better than 0.3 at natural abundance. For labelled mixtures, the coefficient of variation was between 1% at 0.07 atom % excess (APE) for threonine and alanine, and around 10% at 0.03 APE for valine and phenylalanine. The application of irm-LC/MS to the determination of the isotopic enrichment of 13C-threonine in an extract of rat colon mucosa demonstrated a precision of 0.5, or 0.001 atom %.

"A Thin Chip Microsprayer System Coupled To Fourier Transform Ion Cyclotron Resonance Mass Spectrometry For Glycopeptide Screening"
Rapid Commun. Mass Spectrom. 2004 Volume 18, Issue 23 Pages 2913-2920
Laura Bindila, Martin Froesch, Niels Lion, eljka Vukeli, Joël S. Rossier, Hubert H. Girault, Jasna Peter-Katalini*, Alina D. Zamfir*

Abstract: A thin polymer microchip was coupled with a Fourier transform ion cyclotron resonance (FTICR) 9.4 T mass spectrometer and the method was optimized in negative ion mode for glycopeptide screening. The interface between the polymer microchip and FTICR mass spectrometer consists of an in-laboratory conceived and designed mounting system that exhibits robust and controllable alignment of the chip toward the inlet of the mass spectrometer. The particular attribute of the polymer chip coupled to the FTICR mass spectrometer, to achieve an increase in ionization efficiency and sensitivity under the premise of high mass accuracy of detection, is highlighted by the large number of major and minor glycopeptide structures detected and identified in highly heterogeneous mixtures obtained from urine matrices. Glycoforms expressing various saccharide chain lengths ranging from tri- to dodecasaccharide, bearing up to three sialic acid moieties, could be detected and assigned based on the accuracy of the mass measurement (average mass deviation below 6 ppm) of their molecular ions. (-)Thin chipESI-FTICRMS is a potent novel system for glycomic screening of complex mixtures, as demonstrated for identification of singly sialylated O-glycosylated amino acids and peptides from urine matrices, and could be considered for general applicability in the glycoanalytical field.
Microfluidic

"Flow Injection Analysis Mass Spectrometry, A Tool To Investigate The Problems In The Quantitative Analysis Of Hypericin Using Reversed-phase High-performance Liquid Chromatography"
Rapid Commun. Mass Spectrom. 2004 Volume 18, Issue 1 Pages 131-132
Anna Piovan, Raffaella Filippini*, Anna Borsarini, Rosy Caniato

Abstract: The use of flow injection and the comparison with LC/MS have led to reliable quantification of the fractional retained hypericin on the different RP-18 columns tested here. However, from these experiments, we are not able to provide a satisfactory explanation of why hypericin is randomly held on these apparently very similar columns. The choice of column for this analysis is clearly of great importance, and column 5 was the only one that behaved satisfactorily in our hands.

"Flow Injection Of The Lock Mass Standard For Accurate Mass Measurement In Electrospray Ionization Time-of-flight Mass Spectrometry Coupled With Liquid Chromatography"
Rapid Commun. Mass Spectrom. 2003 Volume 17, Issue 13 Pages 1383-1388
Laurence Charles

Abstract: A method of flow injection of the lock mass for accurate mass measurement using electrospray ionization time-of-flight mass spectrometry is described. The reference compound is introduced in the chromatographic effluent via a six-port valve placed post-column, prior to the split connector. Flow injection is performed in such a way that the reference elution peak is superimposed in the total ion current and partially overlaps that of the investigated analyte, allowing independent ionization of the two compounds and thus accurate mass measurement with no ion suppression effects. Different lock mass molecules can be injected in a single analytical run to target various analytes. The performance of this methodology is demonstrated in both isocratic and gradient liquid chromatography modes. The molecular ion of the flow-injected lock mass could also be used as a reference for mass measurement of the in-source fragments of the analytes. Good mass accuracy, within 4 mDa of the theoretical values, was obtained.

"Investigation Of Cytolysin Variants By Peptide Mapping: Enhanced Protein Characterization Using Complementary Ionization And Mass Spectrometric Techniques"
Rapid Commun. Mass Spectrom. 2002 Volume 16, Issue 22 Pages 2094-2101
Stanley M. Stevens Jr., William R. Kem, Laszlo Prokai

Abstract: Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) have been used in conjunction with time-of-flight (TOF) and quadrupole ion trap (IT) mass spectrometry, respectively, to analyze various cytolysin proteins isolated from the sea anemone Stichodactyla helianthus and digested by the protease trypsin. By employing different ionization methods, the subsequent changes in ionization selectivity for the peptides in the digested protein samples resulted in ion abundance variation reflected in the mass spectra. Upon investigation of this variation generated by the two ionization processes, it has been shown in this study that enhanced protein coverage (e.g., >95% for cytolysin III) can be achieved. Additionally, capillary and microbore reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with ESI mass spectrometry (MS) as well as flow injection analysis by nanoflow ESI-MS afforded the necessary limit of detection (LOD) for detailed structural information of the cytolysin proteins by tandem mass spectrometry (MS/MS) methods. It can be concluded that cytolysins II and III correspond to sticholysins I and II, that cytolysin I is a mixture of modified forms of cytolysins II and III, and that cytolysin IV is an incompletely processed precursor of cytolysin III.

"Rapid Quantitation Of Globotriaosylceramide In Human Plasma And Urine: A Potential Application For Monitoring Enzyme Replacement Therapy In Anderson-Fabry Disease"
Rapid Commun. Mass Spectrom. 2002 Volume 16, Issue 16 Pages 1507-1514
Francesca Boscaro, Giuseppe Pieraccini, Giancarlo la Marca, Gianluca Bartolucci, Cristina Luceri, Francesca Luceri, Gloriano Moneti

Abstract: A method for measuring globotriaosylceramide (Gb3, or GL3) levels in plasma and urine of humans affected by Anderson-Fabry disease has been developed. The analyzes are performed using flow injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS). The method is rapid, sensitive and hence suitable for high-throughput analyzes, requiring only a simple 50-fold dilution for the preparation of plasma and urine samples. The detection of the analytes of interest was achieved using a triple quadrupole instrument operating in the multiple reaction monitoring mode. The linearity of the calibration standard responses, the intra- and inter-assay precision, the accuracy and the detection limit of the method were evaluated. The proposed method allows a rapid and accurate assessment of globotriaosylceramide in biological samples. Data obtained from healthy volunteers and Anderson-Fabry affected subjects suggest a potential role for this technique in monitoring the effectiveness of Anderson-Fabry disease therapy. The results obtained in two actual cases treated with enzyme replacement therapy are reported and discussed.

"Determination Of Total Urinary Mercury By On-line Sample Microwave Digestion Followed By Flow Injection Cold Vapor Inductively Coupled Plasma Mass Spectrometry Or Atomic Absorption Spectrometry"
Rapid Commun. Mass Spectrom. 2002 Volume 16, Issue 15 Pages 1432-1439
M. Bettinelli, S. Spezia, A. Ronchi, C. Minoia

Abstract: The total mercury content in urine was determined by inductively coupled plasma mass spectrometry with the so-called cold vapor method after on-line oxidative treatment of the sample in a microwave oven (Fl-MW-CV-ICPMS). Use of a KBr/KBrO3 mixture, microwave digestion, and the final oxidation with KMnO4, assure the complete recovery of the organic forms of Hg which would be difficult to determine otherwise if using only the CV-ICPMS apparatus. Quantitative recoveries were obtained for phenyl Hg chloride (PMC), dimethyl Hg (DMM), Hg acetate (MA) and methyl Hg chloride (MMC). Use of automatic flow injection microwave systems (FI-MW) for sample treatment reduces environmental contamination and allows detection limits suitable for the determination of reference values. Since no certified reference materials were commercially available in the concentration ranges of interest, the accuracy of the proposed procedure has been assessed by analyzing a series of urine samples with two independent techniques, ICP-MS and AAS. When using the FI-MW-CV-ICP-MS technique, the detection limit was assessed at 0.03 mug/L Hg, while with FI-MW-CV-AAS it was 0.2 mug/L Hg. The precision of the method was less than 2-3% for FI-MW-CV-ICP-MS and about 3-5% for FI-MV-CV-AAS at concentrations below 1 mug/L Hg. These results show that ICP-MS can be considered as a reference technique for the determination of total urinary Hg at very low concentrations, such as are present in non-exposed subjects.

"Analysis Of Saccharides In Beer Samples By Flow Injection With Electrospray Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2002 Volume 16, Issue 8 Pages 743-748
Pierluigi Mauri, Markus Minoggio, Paolo Simonetti, Claudio Gardana, Piergiorgio Pietta

Abstract: Saccharides in foods play important roles, as they are essential substrates for fermentation processes. In brewing, the concentration of maltooligosaccharides influences the characteristics of beers and therefore their determination is of great practical interest. Electrospray ionization mass spectrometry (ESI-MS) was applied to identify and characterise maltooligosaccharides in beer samples. The effects due to different cation concentrations and dilution of samples were studied. Furthermore, quantitative analyzes of maltooligosaccharides by means of flow injection ESI-MS (FI/ESI-MS) of 1 µL beer samples (diluted 1000-fold) are described.

"A Rapid, Automated Approach To Optimisation Of Multiple Reaction Monitoring Conditions For Quantitative Bioanalytical Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 20 Pages 1922-1930
David M. Higton

Abstract: An improvement to the procedure for the rapid optimization of mass spectrometry (PROMS), for the development of multiple reaction methods (MRM) for quantitative bioanalytical liquid chromatography/tandem mass spectrometry (LC/MS/MS), is presented. PROMS is an automated protocol that uses flow injection analysis (FIA) and AppleScript (R) to create methods and acquire the data for optimization. The protocol determines the optimum orifice potential, the MRM conditions for each compound, and finally creates the MRM methods needed for sample analysis. The sensitivities of the MRM methods created by PROMS approach those created manually. MRM method development using PROMS currently takes less than three minutes per compound compared to at least fifteen minutes manually. To further enhance throughput, approaches to MRM optimization using one injection per compound, two injections per pool of five compounds and one injection per pool of five compounds have been investigated. No significant difference in the optimized instrumental parameters for MRM methods were found between the original PROMS approach and these new methods, which are up to ten times faster. The time taken for an AppleScript to determine the optimum conditions and build the MRM methods is the same with all approaches.

"Direct Coupling Of A Nano-high-performance Liquid Chromatography Column To An Ion Trap Designed For A Gas Chromatography/mass Spectrometry System"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 17 Pages 1609-1617
Gloriano Moneti, Giuseppe Pieraccini, Gianluca Bartolucci, Gianni Guida, Roberta Seraglia, Pietro Traldi

Abstract: The possibility of direct liquid injection inside an ion trap, designed for a commercial gas chromatography/mass spectrometry (GC/MS) system, has been tested by continuous solution flow and by loop injection. Instrumental parameters such as solution flows and sample concentration, and temperatures of transfer line, ion trap and ion trap housing, have been optimized. Different configurations of the interface capillary have been also considered, and the best results have been obtained by the injection of the solution coaxially with a helium flow. The experimental arrangement leads to the detection of good quality electron (EI) and chemical (CI) ionisation spectra of low to medium polarity compounds, at µM levels. The direct coupling of a nano-HPLC column with the modified transfer line led on one hand to EI spectra which were successfully employed for library searches, and on the other to CI data directly comparable to results achieved by a commercial HPLC/MS system operating under ESI conditions.

"Monitoring The Production Yields Of Vincristine And Vinblastine In Catharanthus Roseus From Somatic Embryogenesis. Semiquantitative Determination By Flow Injection Electrospray Ionization Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 5 Pages 364-369
Donata Favretto, Anna Piovan, Raffaella Filippini, Rosamaria Caniato

Abstract: A semiquantitative determination of two bis-indole antitumor alkaloids, vincristine and vinblastine, has been performed by flow injection electrospray ionization mass spectrometric analysis of the extracts of Catharanthus roseus. Leaves and flowers of two different phenotypes (pink flower and white flower) obtained from somatic embryogenesis were thus examined and compared with the field-grown mother plant. Different amounts of vincristine and vinblastine were detected depending on the examined samples. Copyright

"Continuous Flow Stable Isotope Methods For Study Of δ13C Fractionation During Halomethane Production And Degradation"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 5 Pages 357-363
Robert. M. Kalin, John. T.G Hamilton, David. B. Harper, Laurence G. Miller, Clare Lamb, James. T. Kennedy, Angela Downey, Sean McCauley, Allen H. Goldstein

Abstract: Gas chromatography/mass spectrometry/isotope ratio mass spectrometry (GC/MS/IRMS) methods for delta C-13 measurement of the halomethanes CH3Cl,CH3Br, CH3I and methanethiol (CH3SH) during studies of their biological production, biological degradation, and abiotic reactions are presented. Optimization of gas chromatographic parameters allowed the identification and quantification of CO2, O-2, CH3Cl, CH3Br, CH3I and CH3SH from a single sample, and also the concurrent measurement of delta C-13 for each of the halomethanes and methanethiol. Precision of delta C-13 measurements for halomethane standards decreased (±0.3,±0.5 and±1.3 parts per thousand) with increasing mass (CH3Cl, CH3Br, CH3I, respectively). Given that carbon isotope effects during biological production, biological degradation and some chemical (abiotic) reactions can be as much as 100 parts per thousand, stable isotope analysis offers a precise method to study the global sources and sinks of these halogenated compounds that are of considerable importance to our understanding of stratospheric ozone destruction. Copyright

"Genotyping Short Tandem Repeats Using Flow Injection And Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 5 Pages 348-350
James C. Hannis, David C. Muddiman

Abstract: Characterizing polymerase chain reaction (PCR) amplicons has been accomplished for the first time using flow injection analysis coupled to electrospray ionization mass spectrometry (ESI-MS). The PCR amplicons were amplified at the human tyrosine hydroxylase short tandem repeat locus from an individual homozygotic for the 9.3 allele. One product was amplified using Pfu polymerase and yielded a blunt-ended amplicon of 82 base-pairs (bp) in length. The second PCR product was amplified using Taq polymerase that resulted in an amplicon with cohesive termini of 82 bp plus either mono- or diadenylation. The two PCR amplicons were alternatively injected using a 0.5 µL loop at 2 muM for the Pfu amplicon and 1 muM for the Taq amplicon with a flow rate of 200 nL/min during data acquisition. Both PCR amplicons were accurately identified using mass measurements illustrating the compatibility of ESI-MS for genotyping short tandem repeat sequences and the potential for high-throughput genotyping of large PCR amplicons.

"Validation Of Liquid-liquid Extraction Followed By Flow Injection Negative Ion Electrospray Mass Spectrometry Assay To Topiramate In Human Plasma"
Rapid Commun. Mass Spectrom. 2001 Volume 15, Issue 2 Pages 159-163
Su Chen, Paul M. Carvey

Abstract: This paper describes the development and validation of a method for the quantitative analysis of Topiramate (2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate), a new antiepileptic drug, in human plasma using liquid-liquid extraction followed by flow injection negative ion electrospray mass spectrometry. Using Prednisone (1,4-pregnadiene-17-α,21-diol-3,11,20-trione [10 µg/mL]) as an internal standard, calibration curves for Topiramate were linear over a range of 1 to 30 µg/mL in human plasma and were highly reliable (r2 = 0.9991). The lower limit of quantitation of the assay was 2 µg/mL in human plasma. Precision (%CV <15%) and accuracy (<20%) for both intra- and inter-day validations were satisfactory. The method has been used in clinical pharmacology research.

"Exploratory Pharmacokinetics And Brain Distribution Study Of A Neuropeptide FF Antagonist By Liquid Chromatography/atmospheric Pressure Ionization Tandem Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 24 Pages 2412-2418
Laszlo Prokai, Alevtina D. Zharikova, Tam&aacute;s Jan&aacute;ky, Katalin Prokai-Tatrai

Abstract: Dansyl-Pro-Gln-Arg-NH,, an N-terminally modified tripeptide amide and a putative neuropeptide FF antagonist, was amenable to both positive-ion ESI and APCI, The protonated molecule yielded several fragment ions upon collision-induced dissociation in a quadrupole ion trap instrument for the development of LC/MS/MS assay methods. ESI clearly outperformed APCI in limits of detection, and was the method of choice for coupling with narrow-bore reversed-phase liquid chromatography to assess the phannacokinetic profile and brain concentration of the neuropeptide FF antagonist in experimental animals. While plasma could be analyzed after rapid sample preparation, brain tissue required cleanup (solid phase extraction) and pre-concentration before injection, and the assay was prone to matrix interference. This study indicated a rapid disappearance of dansyl-Pro-Gln-Arg-NH2 from the plasma and the brain, and modest CNS bioavailability after intravenous administration to rats. Copyright

"AutoScan: An Automated Workstation For Rapid Determination Of Mass And Tandem Mass Spectrometry Conditions For Quantitative Bioanalytical Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 21 Pages 2074-2079
Kevin M. Whalen, Katrina J. Rogers, Mark J. Cole, John S. Janiszewski

Abstract: An automated flow injection analysis (FIA) mass spectrometry system (AutoScan) was developed to allow rapid unattended determination of optimal conditions during mass (ms) and tandem mass spectrometry (ms/ms) on new chemical entities (NCEs) arranged in 96-well plates, The 96-well plate Is placed on the deck of a modified Gilson Multiprobe autosampler for injection into a PE Sciex API 2000 triple quadrupole mass spectrometer, A customized software interface is used to create the necessary scan experiments by associating each 96-well plate of NCEs to be scanned with an index file containing data on the identity of each analyte and its expected molecular weight. Analytes are injected four at a time into a custom injection manifold and conventional mass spectra are acquired in both polarities (±) using an alternating positive/negative Q1 scan function. The software determines the optimal polarity and definitive precursor ion for all analytes and uses the results to build the Injection sequence for product ion scanning. The samples are automatically re-injected under MS/MS conditions, and product ion scans that loop among different collision energies are collected for each analyte. The resulting data are processed automatically and the optimal MS/MS transitions for each analyte are selected. A color-coded graphical interface facilitates data review, Any unusual ion transitions or transposition errors made during plate preparation are noted and corrected. Complete MS and MS/MS conditions are obtained for 96 compounds in about one hour and the resulting data are available for download as sample control injection sequence files.
Combinatorial chemistry

"Stable Carbon And Oxygen Isotopic Analysis Of Carbon Monoxide In Natural Waters"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 16 Pages 1507-1512
Urumu Tsunogai, Fumiko Nakagawa, Yosuke Hachisu, Naohiro Yoshida

Abstract: Techniques have been developed to allow on-line simultaneous analysis of concentration and stable isotopic compositions (C-13 and O-18) of dissolved carbon monoxide (CO) in natural water, using continuous-flow isotope ratio mass spectrometry (CF-IRMS), The analytical system consisted sequentially of a He-sparging bottle of water, a gas dryer, CO2-trapping stage using both Ascarite trap and silica-gel packed gas chromatography (GC), on-line oxidation to CO2 using the Schutze reagent, cryofocusing, GC purification using a capillary column and measurement by CF-IRMS, Each sample analysis takes about 40 minutes. The detection limit with delta(13)C standard deviation of 0.5 parts per thousand is 300 pmol and that with delta(18)O deviation of 1.0 parts per thousand is 750 pmol. Analytical blanks associated with these methods are 21±9 pmol, The procedures are evaluated through analyzes of temporally varying concentration and isotopic compositions of CO in an artificial lake on the university campus. The delta(13)C and delta(18)O values of CO showed wide variation in accordance with diurnal variation of CO concentration, probably due to significant isotopic effects during photochemical production and microbial oxidation of CO in the aquatic environment. The delta(13)C and delta(18)O values of CO should be a useful tool in studies of the mechanism and pathways of CO production and consumption in natural waters, Copyright

"On-line Nitrate-δ15N Extracted From Groundwater Determined By Continuous-flow Elemental Analyzer/isotope Ratio Mass Spectrometry"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 14 Pages 1266-1268
R. D. Stickrod II, J. D. Marshall

Abstract: Nitrate-δ(15)N from groundwater samples is determined on an inorganic nitrate derivative using automated, continuous-flow elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). Nitrate is extracted and concentrated based on a recently published ion-exchange resin method. Freeze-dried AgNO3 (0.5-1.5 mg) is packed in sliver-foil cups and combusted within the reactor of an NC2500 elemental analyzer (CE Instruments, Milan, Italy) using its existing reaction scheme for nitrogen and carbon analysis. delta(15)N is determined using a Finnigan MAT DELTA(plus) isotope ratio mass spectrometer (Bremen, Germany). Results are drift-corrected to a AgNO3 working standard that has been calibrated against known AgNO3. Despite high concentrations of carbonate, the precision for all runs is better than 0.10%. The combination of this extraction procedure with commercially available delta(15)N analysis instrumentation offers a precise on-line alternative to existing methods, with considerable reduction in labor and analysis time, Copyright

"A Simple, Practical Methodology For Routine VSMOW/SLAP Normalization Of Water Samples Analyzed By Continuous Flow Methods"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 12 Pages 1044-1046
Stephen T. Nelson

Abstract: Normalization of stable isotope data is important for meaningful inter-laboratory comparisons of data, especially for waters where there may be large natural variations in isotope ratios of oxygen and hydrogen. As a result, large, systematic errors may arise in continuous flow applications without correction, whereas normalization to the VSMOW/SLAP scale can facilitate inter-laboratory comparison and can be accomplished by a simple procedure in which secondary laboratory standards, carefully calibrated, are analyzed along with unknown samples, Delta values for these standards, as analyzed, are plotted against the calibrated values and a linear regression is performed. The resulting equation is applied to unknown samples to achieve the normalization. The 1s standard deviation fur replicate samples by this normalization method using a Finnigan Gasbenchll should be less than or equal to 0.1 parts per thousand. Because samples are analyzed directly against calibrated laboratory standards, this method also alleviates the requirement to carefully calibrate reference gases, to carefully control absolute temperatures for equilibration methods, or to determine H3+ for delta D-VSMOW measurements.

"Detection Of Oxidative Species For 4-phenoxyphenol Derivatives During The Electrospray Ionization Process"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 9 Pages 756-764
Yunhui Wu, Hong Wang

Abstract: Analyses by flow Injection as well as liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) were performed with four 4-phenoxyphenol derivatives. When ambient temperature nitrogen gas was used to facilitate solvent evaporation, [M + H](+), [M + NH4](+), and [2M + NH4](+) ions were observed as the major ions. As the nitrogen gas temperature increased from ambient to 250 and 450°C, [M](+.), [M - 1](+) and [M + 15](+) ions were the predominant ions. Heat-induced oxidation was found to be the primary source for the formation of oxidative species. Aqueous solvents were found to be essential for the formation of the [M + 15](+) ions. The [M](+.) and [M + 15](+) ions were further characterized by tandem mass spectrometry. Based on the MS/MS data, it was proposed that the [M + 15](+) ions were the in-source generated 1,2-quinone ions. Copyright
Derivatization

"Determination Of Methotrexate In Environmental Samples By Solid Phase Extraction And High Performance Liquid Chromatography: Ultraviolet Or Tandem Mass Spectrometry Detection?"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 8 Pages 685-691
Roberta Turci, Giuseppina Micoli, Claudio Minoia

Abstract: In order to assess exposure levels of hospital personnel involved in the preparation and administration of antineoplastic drugs, environmental monitoring should be carried out. Wipe samples, pads, gloves and air samples should be collected at the end of each work shift, properly treated and then analyzed using instrumental techniques which are sufficiently sensitive and specific to detect even trace amounts of drug. In this study, a method using high performance liquid chromatography/tandem mass spectrometry (HPLC/ MS/MS), incorporating solid phase extraction (SPE), was validated for determination of methotrexate (MTX) in wipe and air samples, Each step of the method was first developed and optimized using ultraviolet detection (UV), and afterwards tandem mass spectrometry was used to obtain a lower limit of quantitation when the expected drug level was less than the analytical UV detection limit. SPE enabled a 20-fold pre-concentration of the analyte when using HPLC/UV and a further 30-fold pre-concentration was obtained when analyzing samples by HPLC/MS/MS, For example, the limit of quantitation (LLQ) was lowered from 3000 ng on wipe (direct injection onto an HPLC/UV system) to 5 ng on wipe (SPE plus HPLC/MS/MS), 7-hydroxymethotrexate was used as internal standard to assess precision and accuracy. Copyright

"A Library Of Atmospheric Pressure Ionization Daughter Ion Mass Spectra Based On Wideband Excitation In An Ion Trap Mass Spectrometer"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 5 Pages 349-356
Christian Baumann, Maria A. Cintora, Matthias Eichler, Elisabeth Lifante, Michael Cooke, Anna Przyborowska, John M. Halket

Abstract: A searchable library of MS/MS spectra obtained using a quadrupole ion trap mass spectrometer and electrospray or atmospheric pressure chemical ionization is presented. The application of wideband excitation (activation) and normalized collision energy leads to highly reproducible mass spectra which are searched using the NIST algorithm, Flow injection and LC/MS/MS applications of this powerful technique in the biomedical (diastereoisomeric steroids, morphine glucuronides, isovalerylcarnitine) and environmental (pirimicarb and desmethyl-pirimicarb) areas are described.

"Continuous Flow Infrared Matrix-assisted Laser Desorption/ionization With A Solvent Matrix"
Rapid Commun. Mass Spectrom. 2000 Volume 14, Issue 3 Pages 129-134
Steven J. Lawson, Kermit K. Murray

Abstract: Continuous flow matrix-assisted laser desorption/ionization (MALDI) was demonstrated with infrared laser desorption and an ethanol matrix. A capillary was used to deliver an analyte solution dissolved in ethanol to a metal frit embedded in a sample stage. Typical how rates were 1.7 µL/min. An optical parametric oscillator tuned to 2.8 µm was used for desorption and ionization, and mass analysis was achieved with a 1 m linear time-of-flight mass spectrometer. Flow injection studies were performed with low picomolar quantities of insulin and myoglobin in solutions containing 0.1 to 1.0% glycerol in ethanol, Copyright

"Rapid Approach To The Quantitative Determination Of Topiramate (2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose Sulfamate) In Human Plasma By Liquid-liquid Extraction And Flow Injection Negative-ion Electrospray Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1999 Volume 13, Issue 20 Pages 1980-1984
Su Chen, Paul M. Carvey

Abstract: Topiramate, a sulfamate-substituted monosaccharide (2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopy-ranose sulfamate), is a new antiepileptic drug, which has been approved for adjunctive therapy in adult patients with partial-onset seizures, Liquid-liquid extraction followed by flow injection negative-ion electrospray mass spectrometry was evaluated as a means for the quantitative analysis of Topiramate in human plasma. Prednisone (1,4-pregnadiene-17-α,21-diol-3,11,20-trione [15 µg/mL]) was used as the internal standard because its solubility and molecular weight are similar to those of Topiramate, Calibration curves for Topiramate were linear over a range of 1 to 30 µg/mL plasma (signal-to-noise ratio >4) and were highly reliable (r2 = 0.994), This approach offers several advantages: (i) the extraction of Topiramate from human plasma using chloroform is simple and reproducible; (ii) the quantitative determination of Topiramate, in the presence of an internal standard, by blow-injection negative-ion electrospray mass spectrometry with selected-ion recording, is rapid and accurate and does not require chromatographic separation; (iii) the assay possesses adequate sensitivity (2-25 µg/mL) for the quantitative analysis of Topiramate in plasma from patients.
Quality

"Direct Identification Of Yessotoxin In Shellfish By Liquid Chromatography Coupled With Mass Spectrometry And Tandem Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 19 Pages 1291-1296
Rosa Draisci *, Luigi Giannetti, Luca Lucentini, Emanuele Ferretti, Luca Palleschi, Camilla Marchiafava

Abstract: A new method for the direct identification of yessotoxin (YTX), a polyether compound belonging to the diarrheic shellfish poisoning (DSP) toxins, using liquid chromatography coupled with mass spectrometry and tandem mass spectrometry (LC/MS and LC/MS/MS) is reported. Full-scan ion-spray mass spectra of YTX, as acquired in single MS negative ion mode by flow injection analysis (FIA), showed the most intense ion at m/z 1141, assigned to the [M-2Na+H]-, the ion at m/z 1163, assigned to the [M-Na]- and a signal at m/z 1185, due to the deprotonated mol. [M-H]- of the analyte taken here to be the disodium salt. Collision induced dissociation of the precursor ion at m/z 1141, as obtained by FIA negative tandem mass spectrometry experiments, showed the most intense fragment ions in the higher mass region, at m/z 1061, m/z 924, m/z 855, m/z 713, which are characteristic of the structure of the analyte. Ion-spray reversed phase LC/MS and LC/MS/MS was performed by isocratic elution at 30 µL/min, with a mobile phase of acetonitrile-ammonium acetate 4 mM, 80:20 (v/v), using a 1.0 mm i.d. C18 column. The detection of YTX in Italian shellfish samples collected in 1997 from the Adriatic sea was successfully carried out using this method, permitting demonstration of a false negative result obtained by the official mouse bioassay during routine control monitoring.
Yessotoxin Marine HPLC Mass spectrometry Method comparison

"A New Ultra-high Throughput Method For Characterizing Combinatorial Libraries Incorporating A Multiple Probe Autosampler Coupled With Flow Injection Mass Spectrometry Analysis"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 16 Pages 1123-1129
T. Wang, L. Zeng, T. Strader, L. Burton, Daniel B. Kassel *

Abstract: A new method for ultra-fast flow injection analysis-mass spectrometry (FIA-MS) has been developed. An eight probe autosampler system implemented for FIA-MS analysis of combinatorial libraries synthesized in microtiter plates has enabled sample analysis times to be dramatically reduced as compared to microtiter plate analyzes using single arm autosamplers. Compounds contained within the microtiter plate wells are processed eight at a time, eight samples in under a minute. Using this multiple probe autosampler, it has been possible to process a single microtiter plate in 12 min. To facilitate the data acquisition and processing of the samples, the sample data acquisition list, originally generated for registration of compounds synthesized in a microtiter plate format, was modified using an Excel macro into the format of an injection sample list for mass spectral data acquisition. Further, an automated data processing script was developed to process the multi-injection anal. results. Applications of the probe multiple autosampler to the anal. of combinatorial libraries synthesized in microtiter plates and compounds purified into deep well microtiter plates is presented.
Mass spectrometry Automation Computer Apparatus

"Structural Alteration Study Of α-chloro-α-oximino-4-hydroxyacetophenone By Particle Beam Liquid Chromatography Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 15 Pages 1031-1033
S. K. Huang

Abstract: The structure of -chloro--oximino-4-hydroxyacetophenone (COHAP) can be fully characterized by electron ionization and desorption chemical ionization mass spectrometry through a probe introduction of the sample or by the flow injection of particle beam liquid chromatography/mass spectrometry with tetrahydrofuran/hexane elution. With reversed-phase liquid chromatography, or when a normal-phase diol or silica column was employed with nonaqueous mobile phase for the separation of COHAP from its reaction mixture, however, the compound was detected as its dehydrochlorinated product by particle beam liquid chromatography/mass spectrometry. Our studies show that the liquid chromatographic peak which is regarded as COHAP is actually the p-hydroxybenzoyl hydroxamic acid and p-hydroxybenzoyl nitrile oxide under reversed-phase and normal-phase liquid chromatographic conditions, respectively.
HPLC Mass spectrometry

"An Automated Electro-osmotic Sample Introduction/separation Interface For Automated Electro-osmotic Flow Flow Injection Mass Spectrometry, Infusion Mass Spectrometry And Capillary Electrochromatography Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 14 Pages 947-954
Stephen J. Lane *, Michael G. Tucker

Abstract: A novel automated electro-osmotic flow (EOF) sample introduction and separation interface has been designed, developed and successfully coupled to an electrospray mass spectrometer. The system consists of a small-footprint automated capillary electrochromatography (CEC) injection and separation interface that has an integrated auto sampler and connects to the outside world via a proprietary controller for automated CEC/MS, EOF infusion and flow injection analysis (EOFFIA). The system utilizes a previously described CEC/MS/MS micro-electrospray interface that allows optimization of the spray conditions. Short CEC columns or open capillaries are immobilized in a hollow stainless steel needle that is located in a pincher bar through which injection and running high voltage is applied. The needle assembly is easily removed for ease of column installation and changeover. At the heart of the automated system is a microprocessor-based controller which allows both manual and automated control via a 12-way key pad. The controller provides automatic indexing of a 10 position sample carousel, control of kV supply so that injection and running voltages can be set independently for full flexibility and mass spectrometer synchronizing signals. The design, although currently on a Finnigan TSQ 7000, has been made flexible in both mech. and electronic design to be easily adaptable to other mass spectrometers. Examples of all functions of the system are presented here including rapid flow injection and controllable infusion experiments Simple mixtures could be separated by CEC/MS with great efficiency and sensitivity in a short time. An example of multiple automated anal. runs performed continuously over a period of 10 h are described. We believe this is the first report of a custom built CEC system with an integrated CEC/MS/MS interface that obviates the need for an expensive and unsuitable converted commercial CE system for sample introduction while allowing for a useful degree of automation. This system addresses many of the robustness and redn.-to-practice problems of CEC/MS and will catalyze the development of CEC/MS and allow the systematic optimization and evaluation of the technique.
Mass spectrometry Interface Electroosmotic flow Injection technique Apparatus

"Injection Adaptable Fine Ionization Source ('JaFIS') For Continuous-flow Nano-electrospray"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 9 Pages 551-556
Scott Geromanos, John Philip, Gordon Freckleton, Paul Tempst

Abstract: Nanoelectrospray ('nanoES') tandem mass spectrometry of complex peptide mixtures has become a certified, mostly reliable technique for the identification of proteins. The typical low flow rates of nanoES, the extended anal. times for small samples, high ion transmission and its overall ease-of-use provide important practical advantages for polypeptide covalent microanalysis. We have constructed a modified nanoES ion source that is highly durable and user-friendly, and potentially allows for full auto-sampling operation. The injection adaptable Fine Ionization Source ('JaFIS') can be operated at flow rates of 10^-100 nL per min and with sensitivities in the 25 fmol peptide per µL range. The ion spray needles usually last for days, allowing for standards and multiple samples to be analyzed consecutively under similar conditions. In this configuration, quality controlled needles can also be saved and reused, providing for more consistent and reproducible day-to-day operating conditions. JaFIS-ES also permits sample recovery should any failure occur during anal.
Mass spectrometry Interface

"Proton Affinity Of Peroxyacetyl Nitrate Sampled By Membrane Introduction Mass-spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 6 Pages 328-334
N. Srinivasan, R. G. Cooks*, P. B. Shepson

Abstract: Peroxyacetyl nitrate (PAN) is a fragile, highly reactive molecule which has proven difficult to characterize by mass spectrometry, This study investigates the use of a membrane Introduction system to sample PAN and demonstrates that the molecular ions (+), (-) and M-. can be generated under chemical ionization conditions. Use of tandem mass spectrometry provides characteristic spectre. These capabilities are applied to generate adduct ions of PAN with reference compounds of known proton affinity, Collision induced dissociation of these ions gives, by application of the kinetic method relationship, an estimated value of 191±3 kcal/mol (798±12 kJ/mol) for the proton affinity of PAN. (51 References)
Peroxyacetyl nitrate Mass spectrometry Crown ether Kinetic

"A Comparative Evaluation Of Continuous-flow Fast Atom Bombardment And Ion Spray Ionization Techniques For The Simultaneous Determination Of Alkyltrimethylammonium Surfactants By Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 6 Pages 281-284
Silvia A. Coran *, Massimo Bambagiotti-Alberti, Valerio Giannellini, Gloriano Moneti, Giuseppe Pieraccini, Andrea Raffaelli

Abstract: This study compares the performances of two mass-spectrometric ionization techniques, i.e. fast-atom bombardment (FAB) and ion-spray ionization (ISI), in the simultaneous quantitation of dodecyl-, tetradecyl- and hexadecyltrimethylammonium halides in aqueous media. Continuous-flow FAB and flow injection analysis (FIA)-ISI, both in selected-ion monitoring and selected-reaction monitoring modes, were evaluated. Quantitation was performed by dilution with deuterium-labeled homologues synthesized by a simple procedure. A comparison of the data indicated FIA-ISI as the more sensitive (limit of detection = 10 ppb). Good linearity, precision and accuracy were obtained by the tested techniques in the concentration. range 0.125-4.0 ng µL-1. Hair softeners, commercial surfactant mixtures and hematol. lysing reagents were used as test samples.
Surfactants, alkyltrimethylammonium Commercial product Commercial product Mass spectrometry Mass spectrometry Method comparison

"An Eluent-jet Interface For Chemical Ionization Mass Spectrometry And Coupling Of Microcolumn Liquid Chromatography With Electron Ionization Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1998 Volume 12, Issue 1 Pages 5-10
Reyer J. Dijkstra, Ben L. M. Van Baar, Charles E. Kientz, Wilfried M. A. Niessen, Udo A. Th. Brinkman

Abstract: An improved eluent-jet interface was used to combine flow injection analysis (FIA) and micro-column liquid chromatography (LC) online with mass spectrometry (MS) in the electron ionization (EI) and solvent-independent chemical ionization (CI) modes. Good results were obtained for a series of pesticides and for 2-(diethylamino)ethanol (DEAE), a precursor of the chemical warfare V-agents. When using single-ion monitoring, 50 pg of DEAE could be detected in the CI mode, and a linear calibration plot was obtained in the test range of 50-1000 pg. EI-MS spectra obtained in both FIA and micro-LC experiments were closely analogous to those in conventional mass spectral libraries.
Pesticides 2-Diethylaminoethanol Mass spectrometry Interface

"Rapid Scanning Technique For The Determination Of Optimal Tandem Mass Spectrometric Conditions For Quantitative Analysis"
Rapid Commun. Mass Spectrom. 1997 Volume 11, Issue 6 Pages 593-597
D. L. Hiller, T. J. Zuzel, J. A. Williams, R. O. Cole

Abstract: Many of the challenges posed by the quantitative analysis of drug candidates in biological fluids are met by atmospheric pressure ionization tandem mass spectrometry (MS/MS). However, the development of suitable methodology requires the determination and optimization of many compound-specific instrumental variables. At a minimum, the m/z values of a precursor ion and a product ion, along with the optimum collision energy, must be known in order to construct a suitable method. MS/MS method performance is particularly sensitive to collision energy, which must be near-optimum for each compound analyzed. Conventionally, these instrumental parameters are determined by continuous infusion of a standard solution into the ion source and optimizing each individual parameter. This paper describes the application of a technique based on the triple quadrupole mass spectrometer which streamlines the development of quantitative MS/MS methods. Termed a Q3 CID (collision-induced dissociation) scan, the method involves collection of Q3 spectra with a pressurized collision cell and flow injection sample introduction. Operation in this mode introduces all precursor ions into the collision cell, eliminating the need to perform multiple manual experiments. Data are presented which demonstrate that the majority of the information required to construct an MS/MS quantitation method can be obtained in a single flow injection experiment. Performance of quantitative methods constructed with instrument parameters gathered from positive-ion Q3 CID, compared with that of methods developed using conventional infusion optimization is presented. Limitations and applications particular to bioanalytical quantitation are discussed.
Drugs Mass spectrometry Interface Apparatus Optimization

"Membrane Introduction Mass Spectrometry In A Pilot Plant: Online Monitoring Of Fermentation Broths"
Rapid Commun. Mass Spectrom. 1997 Volume 11, Issue 4 Pages 363-367
Rudolph C. Johnson, N. Srinivasan, R. Graham Cooks*, D. Schell

Abstract: The performance of a membrane introduction mass spectrometry (MIMS) system has been tested under pilot plant conditions. The work employed a Finnigan ITS-40 ion trap instrument, adapted to MIMS experiments by the addition of an external membrane/jet separator interface and packaged to operate in an industrial production environment. A representative sample from a 9000 L fermentation reactor was taken continuously and monitored on-line, using a stainless steel tangential filter as the only sample pretreatment. This filter was capable of withstanding the temperature and pressure of 30 psig steam sterilization as well as the 10^-30 psig operating pressure from a sample stream containing in excess of 10% solids. The filtrate was sampled using a flow injection analysis system which allowed quantification using external standards. Calibration experiments established that the system displayed a linear response to ethanol at concentrations between 1 and 10% by volume. During subsequent on-line experiments, ethanol standard and sample streams were examined alternately. The response of the standard solutions was used to quantitate the response of the sample stream and reduce errors associated with long term instrumental drift. Ethanol concentrations were found to be 2.97±0.07% and were quantitatively in agreement with off-line high-performance liquid chromatographic data. Minor components identified during on-line reactor monitoring included acetic and lactic acid. After one week of off-line operation in the pilot plant, on-line monitoring was continued for a period of four days.
Acetic acid Lactic acid Fermentation broth Mass spectrometry Process monitoring Silicone membrane Method comparison

"High-throughput Electrospray Mass Spectrometry Of Combinatorial Chemistry Racks With Automated Contamination Surveillance And Results Reporting"
Rapid Commun. Mass Spectrom. 1996 Volume 10, Issue 15 Pages 1894-1900
G. Hegy *, E. G&ouml;rlach, R. Richmond, F. Bitsch

Abstract: A computerized flow injection electrospray-ionization/atmospheric-pressure CI MS system is described for the high-throughput analysis of routine combinatorial chemistry samples in 96-well sample racks. Two workstation-controlled Finnigan MAT SSQ 7000 mass spectrometers form the basis of the system. The user interface is built on the existing Sandoz computer system, and consists essentially of ASCII file exchange (by a dedicated file transfer protocol on a data-exchange area of the PATHWORKS network) between the user PC (running DEC Pathworks V4.1 under Windows) and the MS workstation (running the Finnigan Interactive Chemical Information System V8.1.1 under OSF/1 V2.0). The automation is based on the Unix Bourne shell with most of the central routines being written in Perl V5.002. Much attention is paid to automated surveillance for contamination.
Mass spectrometry Computer Interface Automation

"Thin Pervaporation Membranes For Improved Performance In Online Flow Injection Analysis Membrane Introduction Mass-spectrometry"
Rapid Commun. Mass Spectrom. 1996 Volume 10, Issue 7 Pages 751-756
Narasimhan Kasthurikrishnan, R. G. Cooks*, Scott Bauer

Abstract: Characterization of some thin (10-50 µm) and selective (zeolite filled) sheet pervaporation membrane materials for the online analysis of volatile compounds in solution by membrane introduction mass spectrometry and dow injection analysis is reported, A comparison of the membrane performance, both in aqueous (normal) and organic (reverse) phase, is made using a seven-component test mixture and a triple quadrupole mass spectrometer, While no significant difference is observed in the normal phase experiments, reverse phase experiments with the thin membranes showed an improvement in rise times and analysis times by a factor of two, Thus, the thin membranes are more suitable for chemical and petrochemical online process monitoring where the frequency of sampling is of great importance, The thin hydrophobic membranes allow enough water to permeate the membrane for chemical ionization to be performed as an alternative to electron impact provided an ion trap mass spectrometer is used. The detection limits observed for the compounds studied using water as a chemical ionization reagent are similar to those achieved by a two-stage enrichment microporous membrane/jet separator device interfaced to an ion trap mass spectrometer and are in the lower parts-per-billion range for some of the compounds studied (5 ppb for methyl ethyl ketone, 5 ppb for acetone), Thus the thinner hydrophobic membranes offer the unique combination of rapid permeation and low detection limits in chemical ionization experiments with an ion trap.
Mass spectrometry Pervaporation Process monitoring

"Determination Of Aflatoxins In Dust And Urine By Liquid Chromatography/electrospray Ionization Tandem Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1995 Volume 9, Issue 13 Pages 1234-1237
Anders Kussak, Carl-Axel Nilsson, Barbro Andersson, Jim Langridge

Abstract: A liquid chromatography/electrospray ionization tandem mass spectrometry method is described for the determination of aflatoxins B1, B2, G1 and G2. Samples of naturally contaminated airborne dust and spiked urine were cleaned up on immunoaffinity columns and analyzed by liquid chromatography using either mass spectrometry detection or post-column derivatization with bromine and fluorescence detection. With tandem mass spectrometry, detection limits (S/N = 3) calculated as amount ejected on column were: aflatoxin B1 4 pg, B2 4 pg, G1 5 pg, and G2 10 pg. (10 references)
Aflatoxin B1 Aflatoxin B2 Aflatoxin G1 Aflatoxin G2 Particulates Urine HPLC Fluorescence Post-column derivatization Method comparison

"Improved Detection Of Glucuronide And Glutathione Conjugates With Thermospray Ionization Following Esterification"
Rapid Commun. Mass Spectrom. 1994 Volume 8, Issue 5 Pages 371-376
Peter E. Haroldsen, Professor Thomas A. Baillie

Abstract: A series of glucuronide and glutathione conjugates of oestradiol, testosterone, morphine, diethylstilbestrol, phenolphthalein and mycophenolic acids were used. Methyl, n-propyl and n-hexyl esters were formed using the respective alcohols made acidic (0.28 M in HCl) by addition of 20 µL of acetyl chloride per mL of alcohol. A 100 µL portion of acidified alcohol was added to 10^-20 µg of conjugate and heated at 45°C for 45 min. The samples were dried under N2 and the residue reconstituted in methanol/H2O (1:1). Samples (100 µL) were introduced into the mass spectrometer via flow injection (1-1.2 ml/min). The Finnigan TSQ-70 instrument, interfaced with a TSP-II thermospray unit was operated in the full-scan mode from m/z 125-700 every 3 s to obtain mass spectral data (details given). The improvements in absolute abundances of pseudomolecular ions were calculated for each conjugate from the ratio of the maximal [M + H]+ or [M + NH4]+ ion current (background corrected) of the esterified vs. native conjugate on a per-mole basis. For the glucuronide conjugates RSD were 14-118% for the native glucuronides, 12-67% methyl, 11-87% propyl and 15-50% for the hexyl esters. For the glutathione conjugates RSD were 30-108% for native, 11-56% methyl, 13-70% propyl and from 26-60% for the hexyl esters.
Glutathione Glucuronide Biological Mass spectrometry

"Analysis Of Neuropeptides By Perfusion Liquid Chromatography/electrospray Ion-trap Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1994 Volume 8, Issue 4 Pages 333-338
Hung-Yu Lin, Robert D. Voyksner

Abstract: Perfusion high performance liquid chromatography (HPLC) combined with electrospray ion trap mass spectrometry (ITMS) was evaluated for the determination of neuropeptides in plasma. Perfusion HPLC offers the capability of resolving neuropeptides spiked into plasma in 5 min compared to the 30-60 min separations performed on packed capillary C18 columns. Electrospray combined with the ITMS provides the ability to ionize these neuropeptides and mass analyze them with high sensitivity and specificity. Sub-picomole quantities of neuropeptides injected on- column could be specifically detected in a plasma matrix. The electrospray-ITMS mass spectrum of each neuropeptide showed multiply charged ions which could be used to determine or confirm their molecular weights.
Peptides, neuro Blood Plasma Mass spectrometry HPLC Perfusion

"Jet Separator Membrane Introduction Mass Spectrometry For Online Quantitation Of Volatile Organic Compounds In Aqueous Solutions"
Rapid Commun. Mass Spectrom. 1993 Volume 7, Issue 10 Pages 935-942
L. E. Dejarme, S. J. Bauer, R. G. Cooks, F. R. Lauritsen, T. Kotiaho, T. Graf

Abstract: A new technique is described for the direct detection of volatile organic compounds present in aqueous solutions at levels in the parts per trillion range. The sample is enriched in analyte in two consecutive stages; one utilizes a semi-permeable membrane interface and the other a jet separator. The analyte solution is sampled as it flows coaxially over a semi-permeable capillary membrane, the interior of which is continuously purged by helium. The permeate is pneumatically transported to the mass spectrometer via a jet separator, which is used to remove excess helium and water from the analyte vapor stream. Data are reported for two instruments; in one the membrane/jet separator system is interfaced to a single quadrupole mass spectrometer via a custom-built metal jet separator with a variable capillary gap. In the second, an ion-trap mass spectrometer is used in conjunction with a conventional fixed-gap quartz jet separator. Typical analyte response times are 2-5 min at ambient temperature, and flow injection methods are used for sample delivery. Direct comparisons, made under identical instrumental conditions, show that the jet separator system displays even lower detection limits than a conventional direct-insertion membrane probe. Detection limits in the range 30 parts per trillion to a few parts per billion are observed for selected volatile organic compounds and the response is linear over 3 orders of magnitude. [References: 31]
Organic compounds, volatile Water Mass spectrometry Mass spectrometry Mass spectrometry Membrane

"Antisense DNA Oligonucleotides. 1. The Use Of Ionspray Tandem Mass Spectrometry For The Sequence Verification Of Methylphosphonate Oligodeoxyribonucleotides"
Rapid Commun. Mass Spectrom. 1993 Volume 7, Issue 3 Pages 190-194
Timothy R. Baker, Thomas Keough, Roy L. M. Dobson, Timothy A. Riley, Jody A. Hasselfield, P. Eric Hesselberth

Abstract: The sequences of synthetically prepared methylphosphonate oligodeoxyribonucleotides have been verified using ionspray tandem mass spectrometry with sample introduction via flow injection. The technique involves the use of product-ion scans from multiply protonated (4+ and 5+) precursors. Among the ions detected are several series of fragments of different charge states that indicate the base sequence of the intact molecule. Oligomers as large as 18 bases have been successfully characterized.
Oligonucleotides Mass spectrometry

"Flow Injection Thermospray Mass Spectrometry For The Automated Analysis Of Potential Agricultural Chemicals"
Rapid Commun. Mass Spectrom. 1993 Volume 7, Issue 1 Pages 85-91
Mark J. Hayward, Joseph T. Snodgrass, Michael L. Thomson

Abstract: An automated flow injection thermospray MS system is described which has been constructed from commercially available equipment. A mobile phase of acetonitrile - 0.1 M ammonium acetate (3:2) is pumped (1.4 mL min-1) continuously to the spectrometer ion source and portions (10 µL) of sample solution are automatically injected into the carrier stream. Separate sample injections are made when both positive- and negative-ion spectra are obtained. The autosampler, injector and MS are computer-controlled and the system is capable of analyzing 150 samples day-1 providing molecular weight and structural data.
Agricultural Mass spectrometry Computer

"Ion-spray Mass Spectrometry Of Marine Toxins. 3. Analysis Of Paralytic Shellfish Poisoning Toxins By Flow Injection Analysis, Liquid Chromatography - Mass Spectrometry And Capillary Electrophoresis - Mass Spectrometry"
Rapid Commun. Mass Spectrom. 1992 Volume 6, Issue 1 Pages 14-24
S. Pleasance, S. W. Ayer, M. V. Laycock, P. Thibault

Abstract: The cited techniques were used to monitor the purification of saxitoxin, the parent compound in the family of toxins that cause paralytic shellfish poisoning (PSP). The results obtained by flow injection analysis are compared with those by HPLC with post-column oxidation and fluorescence detection. The coupling of LC and capillary electrophoresis with ion-spray MS in the separation of mixtures of PSP toxins and tetrodotoxin is described. Tandem MS gave structural information, and it is shown that isomeric PSP toxins can be distinguished both chromatographically and by MS. (For Part II see Anal. Abstr., 1991, 53, 9H90). Ion-spray mass spectrometry has been used to monitor the purifn. of saxitoxin, the parent compound in the family of toxins responsible for paralytic shellfish poisoning (PSP), from a strain of the dinoflagellate Alexandrium excavatum. Quant. results obtained by flow injection analysis are compared to those obtained by high performance liquid chromatography with post-column oxidation and fluorescence detection. The coupling of liquid chromatography and capillary electrophoresis with ion-spray mass spectrometry is described for the separation of mixtures of PSP toxins and the highly potent pufferfish toxin tetrodotoxin. Tandem mass spectrometry is used to provide the structural information, and the ability to distinguish isomeric PSP toxins both chromatography and mass spectrometrically is demonstrated.
Saxitoxin Marine Mass spectrometry Method comparison

"Analysis Of Peptides And Proteins By Capillary Electrophoresis - Mass Spectrometry Using Acidic Buffers And Coated Capillaries"
Rapid Commun. Mass Spectrom. 1991 Volume 5, Issue 10 Pages 484-490
P. Thibault, C. Paris, S. Pleasance, R. M. Caprioli

Abstract: A newly built capillary electrophoresis - MS interface involving ionspray ionization and a coaxial capillary arrangement was used to separate and determine peptides, tryptic fragments and proteins of mol. wt. up to 80 kDa. The interface provides an efficient means of optimizing and calibrating the mass spectrometer by using flow injection analysis, and minimizes peak broadening. Capillary electrophoretic separation of proteins by using a low-pH buffer and a capillary coated with cationic polymer gave better sensitivity and efficiency as compared with similar analyzes at high pH with uncoated capillaries. Pre-formed cationic species are thereby available for MS detection, and the analysis of proteins with high isoelectric points is possible even at low pH. The ability to conduct electrophoresis of globular proteins under acidic conditions permits conformational changes to be monitored in terms of variations in migration times and concurrent changes in the multi-charged ion envelopes. Relatively small amounts of sample are required and successful compromises between scan speed, scan range and separation efficiency are achieved.
Peptides Proteins Electrophoresis Mass spectrometry Buffer Calibration Interface Optimization Sensitivity Small sample

"Electrospray On Magnetic Instruments"
Rapid Commun. Mass Spectrom. 1989 Volume 3, Issue 8 Pages 255-258
Mark H. Allen, Ivor A. S. Lewis

Abstract: Solutions were prepared in 50% methanol, containing 0.1 M acetic acid or -HCl. Aliquots (0.5 µL) were introduced into a continuous-flow (4 to 10 µL min-1) of solvent (e.g., methanol). The carrier stream entered the electrospray probe, to which of 2 to 3 kV was applied; the ions formed were accelerated by a 2 or 4 kV. Spectra were obtained by scanning with a single-focusing magnetic sector instrument or a double-focusing instrument. The system was applied in the investigation of, e.g., reserpine, bradykinin, arginine, simple modified sugars and more complex carbohydrates.
Arginine Bradykinin Reserpine Carbohydrates Mass spectrometry Organic phase detection

"Comparison Of Fast-atom-bombardment, Thermal-ionization And Inductively Coupled Plasma Mass Spectrometry For The Measurement Of Zinc-64/zinc-67 Stable Isotopes In Human Nutrition Studies"
Rapid Commun. Mass Spectrom. 1989 Volume 3, Issue 6 Pages 203-205
J. Eagles, S. J. Fairweather-Tait, F. A. Mellon, D. E. Portwood, R. Self, A. G&ouml;tz, K. G. Heumann, H. M. Crew

Abstract: Samples of faeces from humans receiving 67Zn in feeding experiments were treated in an autoclave, freeze-dried and ashed at 480°C. The ash was dissolved in concentrated HCl, and Zn was isolated by ion-exchange chromatography. Analysis was completed by fast-atom-bombardment or thermal-ionization MS or by ICP-MS with either continuous-nebulization or flow injection introduction. The 64Zn-to-67Zn ratios obtained are reported. The required precision of 1% (coefficient of variation) was not met by flow injection ICP-MS; the methods were otherwise equally suitable.
Zinc-64 Zinc-67 Human Faeces Mass spectrometry Mass spectrometry Mass spectrometry Isotope ratio Method comparison

"Ion-spray Mass Spectrometry Of Marine Neurotoxins"
Rapid Commun. Mass Spectrom. 1989 Volume 3, Issue 5 Pages 145-150
Michael A. Quilliam, Bruce A. Thomson, George J. Scott, K. W. Michael Siu

Abstract: Ion-spray mass spectrometry was investigated for the analysis of three marine neurotoxins: domoic acid, saxitoxin and tetrodotoxin. All three compounds gave positive-ion spectra with abundant ions of protonated molecules and no significant fragmentation. Domoic acid gave a negative-ion spectrum with a strong [M-H]- ion. Tandem mass spectrometry provided useful fragment-ion spectra for all compounds. Detection limits for flow injection analyzes with selected-ion monitoring were determined to be 30 pg for saxitoxin, 100 pg for domoic acid and 200 pg for tetrodotoxin. Combining liquid chromatography with ion-spray mass spectrometry allowed the determination of domoic acid and some of its isomers in toxic shellfish tissue extracts.
Saxitoxin Domoic acid Tetrodotoxin Marine LC Mass spectrometry Sample preparation Detection limit