Paul Rainville - Academia.edu (original) (raw)

Papers by Paul Rainville

Research paper thumbnail of Study of UltraHigh Performance Supercritical Fluid Chromatography to Measure Free Fatty Acids With Out Fatty Acid Ester Preparation

Journal of Chromatography B

Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b)... more Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b) degree of unsaturation, (c) configuration and position of the double bonds, and (d) the presence of other functionalities. Thus, a fast, simple, and quantitative analytical technique to determine naturally occurring free fatty acids (FFA) in different samples is very important. Just as for saponified acylglycerols, the determination of FFA's has generally been carried out by high resolution gas chromatography (HRGC). The use of an open tubular capillary column coupled with a flame ionization or mass spectrometric detector provides for both high resolution and quantification of FFA's but only after conversion of all free fatty acids to fatty acid methyl esters (FAME) or pentafluorobenzyl esters. Unfortunately, volatilization of labile ester derivatives of mono- and poly-unsaturated FFA's can cause both thermal degradation and isomerization of the fatty acid during HRGC. The e...

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Research paper thumbnail of Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells

PLOS ONE, 2015

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Research paper thumbnail of Integration of microfluidic LC with HRMS for the analysis of analytes in biofluids: past, present and future

Bioanalysis, 2015

Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited s... more Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited sample volumes and allow multiple analyses from one sample. This is particularly attractive in areas where ultrahigh assay sensitivity, low limits of detection and small sample volumes are becoming commonplace. However, implementation of cLC-MS in the bioanalytical-drug metabolism area had been hampered by the lack of commercial instrumentation and the need for experts to operate the system. Recent advances in microfabricated devices such as chip-cube and ion-key technologies offer the potential for true implementation of cLC in the modern laboratory including the benefits of the combination of this type of separation with high-resolution MS.

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Research paper thumbnail of Advances in liquid chromatography coupled to mass spectrometry for metabolic phenotyping

TrAC Trends in Analytical Chemistry, 2014

ABSTRACT We review the separations currently employed in the field of global metabolic profiling ... more ABSTRACT We review the separations currently employed in the field of global metabolic profiling and based on the use of liquid chromatography (LC) coupled to mass spectrometry. Currently, most LC separations are performed using reversed-phase (RP) methods, with hydrophilic interaction chromatography a popular choice for polar compounds that are not well served by the RP mode. The use of ultra-(high)-performance LC [U(H)PLC] is seen to be increasingly replacing conventional high-performance LC (HPLC) in metabonomic/metabolomic applications as its benefits are seen as essential for rapid, high-resolution sample analysis. We discuss alternative, and emerging, methods of sample profiling, based on the miniaturization of HPLC-type separations, or the application of supercritical high-performance and ultra-high-performance chromatographic separation.

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Research paper thumbnail of Comparison of the quantification of a therapeutic protein using nominal and accurate mass MS/MS

Bioanalysis, 2012

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Research paper thumbnail of A method for the direct injection and analysis of small volume human blood spots and plasma extracts containing high concentrations of organic solvents using revered-phase 2D UPLC/MS

The Analyst, 2015

The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data ... more The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data quality, reduce animal usage, and save costs in safety assessment studies. The analysis of these samples presents new challenges for bioanalytical scientists, both in terms of sample processing and analytical sensitivity. The use of two dimensional LC/MS with, at-column-dilution for the direct analysis of highly organic extracts prepared from biological fluids such as dried blood spots and plasma is demonstrated. This technique negated the need to dry down and reconstitute, or dilute samples with water/aqueous buffer solutions, prior to injection onto a reversed-phase LC system. A mixture of model drugs, including bromhexine, triprolidine, enrofloxacin, and procaine were used to test the feasibility of the method. Finally an LC/MS assay for the probe pharmaceutical rosuvastatin was developed from dried blood spots and protein-precipitated plasma. The assays showed acceptable recovery, accuracy and precision according to US FDA guidelines. The resulting analytical method showed an increase in assay sensitivity of up to forty fold as compared to conventional methods by maximizing the amount loaded onto the system and the MS response for the probe pharmaceutical rosuvastatin from small volume samples.

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Research paper thumbnail of Ultrahigh performance supercritical fluid chromatography of lipophilic compounds with application to synthetic and commercial biodiesel

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 6, 2015

Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2μm par... more Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2μm particles and either diode array ultraviolet (UV), evaporative light scattering, (ELSD), or mass spectrometric (MS) detection has been shown to be a valuable technique for the determination of acylglycerols in soybean, corn, sesame, and tobacco seed oils. Excellent resolution on an un-endcapped single C18 column (3.0mm×150mm) with a mobile phase gradient of acetonitrile and carbon dioxide in as little as 10min served greatly as an improvement on first generation packed column SFC instrumentation. Unlike high resolution gas chromatography and high performance liquid chromatography with mass spectrometric detection, UHPSFC/MS was determined to be a superior analytical tool for both separation and detection of mono-, di-, and tri-acylglycerols as well as free glycerol itself in biodiesel without derivatization. Baseline separation of residual tri-, di-, and mono-acylglycerols alongside glycero...

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Research paper thumbnail of Rapid analysis of dried blood spot samples with sub-2-µm LC-MS/MS

Bioanalysis, 2011

The use of dried blood and dried plasma spots for storage and transportation of samples derived f... more The use of dried blood and dried plasma spots for storage and transportation of samples derived from clinical trials holds the promise to reduce cost, simplify storage and shipping as well as reducing animal usage. From the bioanalysts' point of view, these dried-paper samples add an extra layer of complexity to the analysis introducing extra matrix effects from the paper itself and sometimes from antiviral treatments applied to the card. In this article we demonstrate the use of the sub-2-µm particle LC-MS/MS for the bioanalysis of samples derived from a dried blood spot. The higher resolution provided by these small-particle separations allowed for greater resolution of the analyte from the endogenous components in blood samples and from the card-treatment chemicals. The method-development process was enhanced by the use of MS, which could simultaneously acquire full scan and multiple reaction monitoring data, allowing resolution from metabolites and endogenous matrix componen...

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Research paper thumbnail of Investigation of microbore UPLC and nontraditional mobile phase compositions for bioanalytical LC-MS/MS

Bioanalysis, 2012

The movement towards environmentally friendly or green chemistry solutions has gained more promin... more The movement towards environmentally friendly or green chemistry solutions has gained more prominence recently in the scientific community. One way in which scientists can address this issue is to limit the use of hazardous chemicals in their everyday processes. Therefore, the focus of this study was on the utilization of microbore-scale chromatography and nontraditional alcoholic mobile phases as an alternative approach to traditional bioanalytical LC-MS/MS assay parameters. Replacement of the traditional narrowbore LC column with a microbore format reduced solvent consumption and produced a greater than threefold increase in S/N. The nontraditional alcoholic mobile phases, ethanol or isopropanol, produced either greater peak area counts, or S/N, for over half of the compounds evaluated, compared with the traditional organic mobile phases of acetonitrile and methanol. These nontraditional alcoholic mobile phases also showed improved capability in the removal of plasma phospholipid ...

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Research paper thumbnail of Investigation of basic mobile phases with positive ESI LC-MS for metabonomics studies

Bioanalysis, 2012

Accurate mass based LC-MS combined with statistical analysis is established as a core analytical ... more Accurate mass based LC-MS combined with statistical analysis is established as a core analytical technology for metabonomic studies. This is primarily due to the specificity, sensitivity and structural elucidation capabilities of the technology. The vast majority of these studies are performed using acidic-based mobile phases in combination with positive ESI mode LC-MS. Recent studies have investigated the use of highly basic pH mobile phases (>10 pH units) in bioanalytical studies that utilize positive ESI mode LC-MS. This non-traditional combination has been shown to improve analyte retention, chromatographic peak shape, and S/N for a variety of probe pharmaceutical compounds in biofluid samples. The incorporation of basic pH mobile phases resulted in increased retention for analytes that where comparatively weakly retained by a traditional acidic-modified mobile phase. Increased resolution of isomers, which otherwise co-eluted under acidic conditions, was observed. Moreover, t...

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Research paper thumbnail of A rapid ultra-performance liquid chromatography/tandem mass spectrometric methodology for the in vitro analysis of Pooled and Cocktail cytochrome P450 assays

Rapid Communications in Mass Spectrometry, 2010

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Research paper thumbnail of The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry

Rapid Communications in Mass Spectrometry, 2006

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Research paper thumbnail of UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation

Rapid Communications in Mass Spectrometry, 2006

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Research paper thumbnail of Addressing the analytical throughput challenges in ADME screening using rapid ultra-performance liquid chromatography/tandem mass spectrometry methodologies

Rapid Communications in Mass Spectrometry, 2008

High-throughput ADME screening for compound drug development properties has become an essential p... more High-throughput ADME screening for compound drug development properties has become an essential part of the modern drug discovery process, allowing more informed decisions to be made on the best compounds to take forward in the discovery/development process. This however is a time-consuming process requiring multiple tests to be performed, demanding a significant amount of liquid chromatography/mass spectrometry (LC/MS) instrument time. This article focuses on the use of sub-2 microm porous particle LC coupled to tandem quadrupole MS/MS mass spectrometry for the rapid screening of ADME properties. Using this approach analysis times from 30 s to 1 min were achievable allowing analysis times to be cut by 80%. The use of the small particles coupled to high flow rates allowed for sufficient resolution, even with very short analysis time, to resolve the analytes of interest from similar compounds that would interfere with the assay. The use of dedicated, intelligent, software packages allowed for the user-free generation of MS/MS conditions and the processing of the data.

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Research paper thumbnail of Sub one minute inhibition assays for the major cytochrome P450 enzymes utilizing ultra-performance liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry, 2008

The measurement of cytochrome P450 (CYP450) isoenzyme inhibition is often done during evaluation ... more The measurement of cytochrome P450 (CYP450) isoenzyme inhibition is often done during evaluation of new chemical entities in drug discovery. Typical assay protocol consists of multiple CYP450 probe substrates incubated with selected drug candidates and CYP450. Results of the assay, the amount of probe substrate metabolite formed with respect to control, are used to determine the level of interaction. Liquid chromatography utilizing columns packed with sub-2-micron particles have been shown to provide up to 8X faster analysis time and 3X increases in sensitivity over traditional high-performance liquid chromatography (HPLC). The work presented here shows the development of a high-throughput, sub-2-micron particle LC method coupled with tandem quadrupole mass spectrometry for the rapid analysis of six CYP450 probe substrate metabolites in 30s.

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Research paper thumbnail of High-temperature ultra-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry applied to ibuprofen metabolites in human urine

Rapid Communications in Mass Spectrometry, 2007

The application of sub-2 microm porous particle liquid chromatography (LC) operated at elevated t... more The application of sub-2 microm porous particle liquid chromatography (LC) operated at elevated temperatures, coupled with time-of-flight mass spectrometry (MS), to the separation and identification of metabolites of ibuprofen present in human urine following oral administrations is illustrated. The LC/MS system generated a high-resolution analytical separation that, with an analysis time of 20 min, provided a peak capacity in the order of ca. 350. Using this system a total of nine glucuronides of the drug and its metabolites were detected, including a number of isomeric acyl glucuronides of ibuprofen itself, a side-chain-oxidized carboxylic acid acyl glucuronide and a number of acyl glucuronides of various hydroxylated metabolites. The identities of the metabolites were confirmed by their accurate mass values and the presence of the common fragment ions from ibuprofen.

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Research paper thumbnail of The rapid detection and identification of the impurities of simvastatin using high resolution sub 2 μm particle LC coupled to hybrid quadrupole time of flight MS operating with alternating high–low collision energy

Journal of Separation Science, 2007

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Research paper thumbnail of The application of small porous particles, high temperatures, and high pressures to generate very high resolution LC and LC/MS separations

Journal of Separation Science, 2007

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Research paper thumbnail of Novel Application of Reversed-Phase UPLC-oaTOF-MS for Lipid Analysis in Complex Biological Mixtures:  A New Tool for Lipidomics

Journal of Proteome Research, 2007

Ultra-Performance LC (UPLC) utilizing sub-2-mum porous stationary phase particles operating with ... more Ultra-Performance LC (UPLC) utilizing sub-2-mum porous stationary phase particles operating with high linear velocities at pressures >9000 psi was coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry and successfully employed for the rapid separation of lipids from complex matrices. The UPLC system produced information-rich chromatograms with typical measured peak widths of 3 s at peak base, generating peak capacities in excess of 200 in 10 min. Further UPLC coupled with MSE technology provided parent and fragment mass information of lipids in one chromatographic run, thus, providing an attractive alternative to current LC methods for targeted lipid analysis as well as lipidomic studies.

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Research paper thumbnail of Comprehensive investigation of the influence of acidic, basic, and organic mobile phase compositions on bioanalytical assay sensitivity in positive ESI mode LC/MS/MS

Journal of Pharmaceutical and Biomedical Analysis, 2012

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Research paper thumbnail of Study of UltraHigh Performance Supercritical Fluid Chromatography to Measure Free Fatty Acids With Out Fatty Acid Ester Preparation

Journal of Chromatography B

Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b)... more Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b) degree of unsaturation, (c) configuration and position of the double bonds, and (d) the presence of other functionalities. Thus, a fast, simple, and quantitative analytical technique to determine naturally occurring free fatty acids (FFA) in different samples is very important. Just as for saponified acylglycerols, the determination of FFA's has generally been carried out by high resolution gas chromatography (HRGC). The use of an open tubular capillary column coupled with a flame ionization or mass spectrometric detector provides for both high resolution and quantification of FFA's but only after conversion of all free fatty acids to fatty acid methyl esters (FAME) or pentafluorobenzyl esters. Unfortunately, volatilization of labile ester derivatives of mono- and poly-unsaturated FFA's can cause both thermal degradation and isomerization of the fatty acid during HRGC. The e...

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Research paper thumbnail of Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells

PLOS ONE, 2015

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Integration of microfluidic LC with HRMS for the analysis of analytes in biofluids: past, present and future

Bioanalysis, 2015

Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited s... more Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited sample volumes and allow multiple analyses from one sample. This is particularly attractive in areas where ultrahigh assay sensitivity, low limits of detection and small sample volumes are becoming commonplace. However, implementation of cLC-MS in the bioanalytical-drug metabolism area had been hampered by the lack of commercial instrumentation and the need for experts to operate the system. Recent advances in microfabricated devices such as chip-cube and ion-key technologies offer the potential for true implementation of cLC in the modern laboratory including the benefits of the combination of this type of separation with high-resolution MS.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Advances in liquid chromatography coupled to mass spectrometry for metabolic phenotyping

TrAC Trends in Analytical Chemistry, 2014

ABSTRACT We review the separations currently employed in the field of global metabolic profiling ... more ABSTRACT We review the separations currently employed in the field of global metabolic profiling and based on the use of liquid chromatography (LC) coupled to mass spectrometry. Currently, most LC separations are performed using reversed-phase (RP) methods, with hydrophilic interaction chromatography a popular choice for polar compounds that are not well served by the RP mode. The use of ultra-(high)-performance LC [U(H)PLC] is seen to be increasingly replacing conventional high-performance LC (HPLC) in metabonomic/metabolomic applications as its benefits are seen as essential for rapid, high-resolution sample analysis. We discuss alternative, and emerging, methods of sample profiling, based on the miniaturization of HPLC-type separations, or the application of supercritical high-performance and ultra-high-performance chromatographic separation.

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Research paper thumbnail of Comparison of the quantification of a therapeutic protein using nominal and accurate mass MS/MS

Bioanalysis, 2012

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A method for the direct injection and analysis of small volume human blood spots and plasma extracts containing high concentrations of organic solvents using revered-phase 2D UPLC/MS

The Analyst, 2015

The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data ... more The emergence of micro sampling techniques holds great potential to improve pharmacokinetic data quality, reduce animal usage, and save costs in safety assessment studies. The analysis of these samples presents new challenges for bioanalytical scientists, both in terms of sample processing and analytical sensitivity. The use of two dimensional LC/MS with, at-column-dilution for the direct analysis of highly organic extracts prepared from biological fluids such as dried blood spots and plasma is demonstrated. This technique negated the need to dry down and reconstitute, or dilute samples with water/aqueous buffer solutions, prior to injection onto a reversed-phase LC system. A mixture of model drugs, including bromhexine, triprolidine, enrofloxacin, and procaine were used to test the feasibility of the method. Finally an LC/MS assay for the probe pharmaceutical rosuvastatin was developed from dried blood spots and protein-precipitated plasma. The assays showed acceptable recovery, accuracy and precision according to US FDA guidelines. The resulting analytical method showed an increase in assay sensitivity of up to forty fold as compared to conventional methods by maximizing the amount loaded onto the system and the MS response for the probe pharmaceutical rosuvastatin from small volume samples.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Ultrahigh performance supercritical fluid chromatography of lipophilic compounds with application to synthetic and commercial biodiesel

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 6, 2015

Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2μm par... more Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2μm particles and either diode array ultraviolet (UV), evaporative light scattering, (ELSD), or mass spectrometric (MS) detection has been shown to be a valuable technique for the determination of acylglycerols in soybean, corn, sesame, and tobacco seed oils. Excellent resolution on an un-endcapped single C18 column (3.0mm×150mm) with a mobile phase gradient of acetonitrile and carbon dioxide in as little as 10min served greatly as an improvement on first generation packed column SFC instrumentation. Unlike high resolution gas chromatography and high performance liquid chromatography with mass spectrometric detection, UHPSFC/MS was determined to be a superior analytical tool for both separation and detection of mono-, di-, and tri-acylglycerols as well as free glycerol itself in biodiesel without derivatization. Baseline separation of residual tri-, di-, and mono-acylglycerols alongside glycero...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Rapid analysis of dried blood spot samples with sub-2-µm LC-MS/MS

Bioanalysis, 2011

The use of dried blood and dried plasma spots for storage and transportation of samples derived f... more The use of dried blood and dried plasma spots for storage and transportation of samples derived from clinical trials holds the promise to reduce cost, simplify storage and shipping as well as reducing animal usage. From the bioanalysts' point of view, these dried-paper samples add an extra layer of complexity to the analysis introducing extra matrix effects from the paper itself and sometimes from antiviral treatments applied to the card. In this article we demonstrate the use of the sub-2-µm particle LC-MS/MS for the bioanalysis of samples derived from a dried blood spot. The higher resolution provided by these small-particle separations allowed for greater resolution of the analyte from the endogenous components in blood samples and from the card-treatment chemicals. The method-development process was enhanced by the use of MS, which could simultaneously acquire full scan and multiple reaction monitoring data, allowing resolution from metabolites and endogenous matrix componen...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Investigation of microbore UPLC and nontraditional mobile phase compositions for bioanalytical LC-MS/MS

Bioanalysis, 2012

The movement towards environmentally friendly or green chemistry solutions has gained more promin... more The movement towards environmentally friendly or green chemistry solutions has gained more prominence recently in the scientific community. One way in which scientists can address this issue is to limit the use of hazardous chemicals in their everyday processes. Therefore, the focus of this study was on the utilization of microbore-scale chromatography and nontraditional alcoholic mobile phases as an alternative approach to traditional bioanalytical LC-MS/MS assay parameters. Replacement of the traditional narrowbore LC column with a microbore format reduced solvent consumption and produced a greater than threefold increase in S/N. The nontraditional alcoholic mobile phases, ethanol or isopropanol, produced either greater peak area counts, or S/N, for over half of the compounds evaluated, compared with the traditional organic mobile phases of acetonitrile and methanol. These nontraditional alcoholic mobile phases also showed improved capability in the removal of plasma phospholipid ...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Investigation of basic mobile phases with positive ESI LC-MS for metabonomics studies

Bioanalysis, 2012

Accurate mass based LC-MS combined with statistical analysis is established as a core analytical ... more Accurate mass based LC-MS combined with statistical analysis is established as a core analytical technology for metabonomic studies. This is primarily due to the specificity, sensitivity and structural elucidation capabilities of the technology. The vast majority of these studies are performed using acidic-based mobile phases in combination with positive ESI mode LC-MS. Recent studies have investigated the use of highly basic pH mobile phases (>10 pH units) in bioanalytical studies that utilize positive ESI mode LC-MS. This non-traditional combination has been shown to improve analyte retention, chromatographic peak shape, and S/N for a variety of probe pharmaceutical compounds in biofluid samples. The incorporation of basic pH mobile phases resulted in increased retention for analytes that where comparatively weakly retained by a traditional acidic-modified mobile phase. Increased resolution of isomers, which otherwise co-eluted under acidic conditions, was observed. Moreover, t...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A rapid ultra-performance liquid chromatography/tandem mass spectrometric methodology for the in vitro analysis of Pooled and Cocktail cytochrome P450 assays

Rapid Communications in Mass Spectrometry, 2010

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry

Rapid Communications in Mass Spectrometry, 2006

Bookmarks Related papers MentionsView impact

Research paper thumbnail of UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation

Rapid Communications in Mass Spectrometry, 2006

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Addressing the analytical throughput challenges in ADME screening using rapid ultra-performance liquid chromatography/tandem mass spectrometry methodologies

Rapid Communications in Mass Spectrometry, 2008

High-throughput ADME screening for compound drug development properties has become an essential p... more High-throughput ADME screening for compound drug development properties has become an essential part of the modern drug discovery process, allowing more informed decisions to be made on the best compounds to take forward in the discovery/development process. This however is a time-consuming process requiring multiple tests to be performed, demanding a significant amount of liquid chromatography/mass spectrometry (LC/MS) instrument time. This article focuses on the use of sub-2 microm porous particle LC coupled to tandem quadrupole MS/MS mass spectrometry for the rapid screening of ADME properties. Using this approach analysis times from 30 s to 1 min were achievable allowing analysis times to be cut by 80%. The use of the small particles coupled to high flow rates allowed for sufficient resolution, even with very short analysis time, to resolve the analytes of interest from similar compounds that would interfere with the assay. The use of dedicated, intelligent, software packages allowed for the user-free generation of MS/MS conditions and the processing of the data.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Sub one minute inhibition assays for the major cytochrome P450 enzymes utilizing ultra-performance liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry, 2008

The measurement of cytochrome P450 (CYP450) isoenzyme inhibition is often done during evaluation ... more The measurement of cytochrome P450 (CYP450) isoenzyme inhibition is often done during evaluation of new chemical entities in drug discovery. Typical assay protocol consists of multiple CYP450 probe substrates incubated with selected drug candidates and CYP450. Results of the assay, the amount of probe substrate metabolite formed with respect to control, are used to determine the level of interaction. Liquid chromatography utilizing columns packed with sub-2-micron particles have been shown to provide up to 8X faster analysis time and 3X increases in sensitivity over traditional high-performance liquid chromatography (HPLC). The work presented here shows the development of a high-throughput, sub-2-micron particle LC method coupled with tandem quadrupole mass spectrometry for the rapid analysis of six CYP450 probe substrate metabolites in 30s.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of High-temperature ultra-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry applied to ibuprofen metabolites in human urine

Rapid Communications in Mass Spectrometry, 2007

The application of sub-2 microm porous particle liquid chromatography (LC) operated at elevated t... more The application of sub-2 microm porous particle liquid chromatography (LC) operated at elevated temperatures, coupled with time-of-flight mass spectrometry (MS), to the separation and identification of metabolites of ibuprofen present in human urine following oral administrations is illustrated. The LC/MS system generated a high-resolution analytical separation that, with an analysis time of 20 min, provided a peak capacity in the order of ca. 350. Using this system a total of nine glucuronides of the drug and its metabolites were detected, including a number of isomeric acyl glucuronides of ibuprofen itself, a side-chain-oxidized carboxylic acid acyl glucuronide and a number of acyl glucuronides of various hydroxylated metabolites. The identities of the metabolites were confirmed by their accurate mass values and the presence of the common fragment ions from ibuprofen.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The rapid detection and identification of the impurities of simvastatin using high resolution sub 2 μm particle LC coupled to hybrid quadrupole time of flight MS operating with alternating high–low collision energy

Journal of Separation Science, 2007

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The application of small porous particles, high temperatures, and high pressures to generate very high resolution LC and LC/MS separations

Journal of Separation Science, 2007

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Novel Application of Reversed-Phase UPLC-oaTOF-MS for Lipid Analysis in Complex Biological Mixtures:  A New Tool for Lipidomics

Journal of Proteome Research, 2007

Ultra-Performance LC (UPLC) utilizing sub-2-mum porous stationary phase particles operating with ... more Ultra-Performance LC (UPLC) utilizing sub-2-mum porous stationary phase particles operating with high linear velocities at pressures >9000 psi was coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry and successfully employed for the rapid separation of lipids from complex matrices. The UPLC system produced information-rich chromatograms with typical measured peak widths of 3 s at peak base, generating peak capacities in excess of 200 in 10 min. Further UPLC coupled with MSE technology provided parent and fragment mass information of lipids in one chromatographic run, thus, providing an attractive alternative to current LC methods for targeted lipid analysis as well as lipidomic studies.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Comprehensive investigation of the influence of acidic, basic, and organic mobile phase compositions on bioanalytical assay sensitivity in positive ESI mode LC/MS/MS

Journal of Pharmaceutical and Biomedical Analysis, 2012

Bookmarks Related papers MentionsView impact