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Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
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A validated method for the determination of nicotine, cotinine, trans‐3′‐Hydroxycotinine, and norcotinine in human plasma using solid‐phase extraction and liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometry
Journal of Mass Spectrometry, 2020Co-Authors: Marilyn A HuestisAbstract:A liquid chromatographic-mass spectrometric method for the simultaneous determination of nicotine, cotinine, trans-3′-Hydroxycotinine, and norcotinine in human plasma was developed and validated. Analytes and deuterated internal standards were extracted from human plasma using solid-phase extraction and analyzed by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometric detection with selected ion monitoring (SIM). Limits of detection and quantification were 1.0 and 2.5 ng/ml, respectively, for all analytes. Linearity ranged from 2.5 to 500 ng/ml of human plasma using a weighting factor of 1/x; correlation coefficients for the calibration curves were > 0.99. Intra- and inter-assay precision and accuracy were < 15.0%. Recoveries were 108.2–110.8% nicotine, 95.8–108.7% cotinine, 90.5–99.5% trans-3′-Hydroxycotinine, and 99.5–109.5% norcotinine. The method was also partially validated in bovine serum, owing to the difficulty of obtaining nicotine-free human plasma for the preparation of calibrators and quality control (QC) samples. This method proved to be robust and accurate for the quantification of nicotine, cotinine, trans-3′-Hydroxycotinine, and norcotinine in human plasma collected in clinical studies of acute nicotine effects on brain activity and on the development of neonates of maternal smokers. Copyright © 2006 John Wiley & Sons, Ltd.
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nicotine metabolite ratio 3 Hydroxycotinine cotinine in plasma and urine by different analytical methods and laboratories implications for clinical implementation
Cancer Epidemiology Biomarkers & Prevention, 2015Co-Authors: Sharon E Murphy, Marilyn A Huestis, Julie Anne Tanner, Maria Novalen, Peter Jatlow, Jaakko Kaprio, Aino Kankaanpaa, Laurence Galanti, Cristiana StefanAbstract:The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-Hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers.Plasma (n = 35) and urine (n = 35) samples were sent to eight different laboratories, which used similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods.Measures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios, 0.82-1.16) and were highly correlated (all Pearson r > 0.96, P < 0.0001). Measures of urinary NMR were in relatively weaker agreement (ratios 0.62-1.71) and less strongly correlated (Pearson r values of 0.66-0.98, P < 0.0001) between different methods. Plasma and urinary COT and 3HC concentrations, while weaker than NMR, also showed good agreement in plasma, which was better than that in urine, as was observed for NMR.Plasma is a very reliable biologic source for the determination of NMR, robust to differences in these analytical protocols or assessment site.Together this indicates a reduced need for differential interpretation of plasma NMR results based on the approach used, allowing for direct comparison of different studies.
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Nicotine Metabolite Ratio (3-Hydroxycotinine/Cotinine) in Plasma and Urine by Different Analytical Methods and Laboratories: Implications for Clinical Implementation.
Cancer Epidemiology Biomarkers & Prevention, 2015Co-Authors: Julie Anne Tanner, Sharon E Murphy, Marilyn A Huestis, Maria Novalen, Peter Jatlow, Jaakko Kaprio, Aino Kankaanpaa, Laurence Galanti, Cristiana Stefan, Tony P. GeorgeAbstract:The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-Hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers.Plasma (n = 35) and urine (n = 35) samples were sent to eight different laboratories, which used similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods.Measures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios, 0.82-1.16) and were highly correlated (all Pearson r > 0.96, P < 0.0001). Measures of urinary NMR were in relatively weaker agreement (ratios 0.62-1.71) and less strongly correlated (Pearson r values of 0.66-0.98, P < 0.0001) between different methods. Plasma and urinary COT and 3HC concentrations, while weaker than NMR, also showed good agreement in plasma, which was better than that in urine, as was observed for NMR.Plasma is a very reliable biologic source for the determination of NMR, robust to differences in these analytical protocols or assessment site.Together this indicates a reduced need for differential interpretation of plasma NMR results based on the approach used, allowing for direct comparison of different studies.
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simultaneous quantification of nicotine cotinine trans 3 Hydroxycotinine norcotinine and mecamylamine in human urine by liquid chromatography tandem mass spectrometry
Clinica Chimica Acta, 2012Co-Authors: Karl B Scheidweiler, Diaa M. Shakleya, Marilyn A HuestisAbstract:Abstract Background Mecamylamine is a nicotine antagonist under investigation in combination with nicotine replacement for smoking treatment. Methods A simple, rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying nicotine, cotinine, trans-3′-Hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was performed on a Synergi PolarRP column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime. Analytes were monitored by positive mode electrospray ionization and multiple reaction monitoring mass spectrometry. Results Linear dynamic ranges were 1–500 ng/ml for nicotine and norcotinine, 0.5–500 ng/ml for trans-3′-Hydroxycotinine, 0.2–500 ng/ml for cotinine, and 0.1–100 ng/ml for mecamylamine; correlation coefficients were consistently greater than 0.99, and all calibrator concentrations were within 20% of target. Extensive endogenous and exogenous interferences were evaluated. At 3 concentrations spanning the linear dynamic range of the assay, mean extraction efficiencies from urine were 55.1–109.1% with analytical recovery (bias) 82.0–118.7% and total imprecision of 0.7–9.1%. Analytes were stable for 24 h at room temperature, 72 h at 4 °C, 72 h in autosampler at 15 °C and after three freeze/thaw cycles. Conclusion This method is useful for monitoring mecamylamine, nicotine and nicotine metabolites in smoking cessation and other clinical nicotine research.
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Simultaneous quantification of nicotine, cotinine, trans-3'-Hydroxycotinine, norcotinine and mecamylamine in human urine by liquid chromatography-tandem mass spectrometry.
Clinica chimica acta; international journal of clinical chemistry, 2012Co-Authors: Karl B Scheidweiler, Diaa M. Shakleya, Marilyn A HuestisAbstract:Mecamylamine is a nicotine antagonist under investigation in combination with nicotine replacement for smoking treatment. A simple, rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying nicotine, cotinine, trans-3'-Hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was performed on a Synergi PolarRP column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime. Analytes were monitored by positive mode electrospray ionization and multiple reaction monitoring mass spectrometry. Linear dynamic ranges were 1-500 ng/ml for nicotine and norcotinine, 0.5-500 ng/ml for trans-3'-Hydroxycotinine, 0.2-500 ng/ml for cotinine, and 0.1-100 ng/ml for mecamylamine; correlation coefficients were consistently greater than 0.99, and all calibrator concentrations were within 20% of target. Extensive endogenous and exogenous interferences were evaluated. At 3 concentrations spanning the linear dynamic range of the assay, mean extraction efficiencies from urine were 55.1-109.1% with analytical recovery (bias) 82.0-118.7% and total imprecision of 0.7-9.1%. Analytes were stable for 24h at room temperature, 72 h at 4 °C, 72 h in autosampler at 15 °C and after three freeze/thaw cycles. This method is useful for monitoring mecamylamine, nicotine and nicotine metabolites in smoking cessation and other clinical nicotine research. Published by Elsevier B.V.
Neal L Benowitz - One of the best experts on this subject based on the ideXlab platform.
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variation in trans 3 Hydroxycotinine glucuronidation does not alter the nicotine metabolite ratio or nicotine intake
PLOS ONE, 2013Co-Authors: Qian Zhou, Neal L Benowitz, Jasjit S Ahluwalia, Rachel F TyndaleAbstract:Background CYP2A6 metabolizes nicotine to its primary metabolite cotinine and also mediates the metabolism of cotinine to trans-3′-Hydroxycotinine (3HC). The ratio of 3HC to cotinine (the “nicotine metabolite ratio”, NMR) is an in vivo marker for the rate of CYP2A6 mediated nicotine metabolism, and total nicotine clearance, and has been associated with differences in numerous smoking behaviors. The clearance of 3HC, which affects the NMR, occurs via renal excretion and metabolism by UGT2B17, and possibly UGT2B10, to 3HC-glucuronide. We investigated whether slower 3HC glucuronidation alters NMR, altering its ability to predict CYP2A6 activity and reducing its clinical utility.
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High dose transdermal nicotine for fast metabolizers of nicotine: a proof of concept placebo-controlled trial.
Nicotine & Tobacco Research, 2012Co-Authors: Robert A. Schnoll, Rachel F Tyndale, E. Paul Wileyto, Frank T. Leone, Neal L BenowitzAbstract:Introduction: Smokers with a faster rate of nicotine metabolism, estimated using the ratio of 3′-Hydroxycotinine (3-HC) to cotinine, have lower plasma nicotine levels and are more likely to relapse with 21 mg nicotine patch therapy, than smokers with slower rates of nicotine metabolism. Thus, faster metabolizers of nicotine may require a higher nicotine patch dose to achieve cessation.
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determination of the nicotine metabolites cotinine and trans 3 Hydroxycotinine in biologic fluids of smokers and non smokers using liquid chromatography tandem mass spectrometry biomarkers for tobacco smoke exposure and for phenotyping cytochrome p45
Journal of Chromatography B, 2011Co-Authors: Peyton Jacob, Lisa Yu, Minjiang Duan, Lita Ramos, Olivia Yturralde, Neal L BenowitzAbstract:Abstract The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3′-Hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography–tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3′-Hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1 ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented.
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Determination of the Nicotine Metabolites Cotinine and Trans-3′-Hydroxycotinine in Biologic fluids of Smokers and Non-Smokers using Liquid Chromatography - Tandem Mass Spectrometry: Biomarkers for Tobacco Smoke Exposure and for Phenotyping Cytochrome
Journal of Chromatography B, 2011Co-Authors: Peyton Jacob, Lisa Yu, Minjiang Duan, Lita Ramos, Olivia Yturralde, Neal L BenowitzAbstract:Abstract The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3′-Hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography–tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3′-Hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1 ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented.
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Chinese “Herbal” Cigarettes Are as Carcinogenic and Addictive as Regular Cigarettes
Cancer Epidemiology Biomarkers & Prevention, 2009Co-Authors: Jie Yang, Neal L Benowitz, Gonghuan Yang, Maciej L. Goniewicz, Stanton A. GlantzAbstract:Objective: To examine the Chinese tobacco industry's claim that herbal cigarettes are less harmful than regular cigarettes. Methods: The study design was a cross-sectional survey. One hundred thirty-five herbal cigarette smokers and 143 regular smokers from one city in China completed a questionnaire on smoking behavior and provided a urine sample. The main outcome measures were cotinine and trans -3′-Hydroxycotinine in all samples, and polycyclic aromatic hydrocarbon metabolites (PAH; 1-hydroxypyrene, naphthols, hydroxyfluorenes, and hydroxyphnanthrenes) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and NNAL-glucuronide in randomly selected 98 samples (47 from the herbal smokers' group and 51 from the regular smokers' group). Values were normalized by creatinine to correct for possible variability introduced by dilution or concentration of the urine. Results: Health concern was among the main reasons that smokers switched to herbal cigarettes from regular cigarettes. Smokers reported increased consumption after switching to herbal cigarettes from regular cigarettes. For all the four markers analyzed (cotinine, trans -3′-Hydroxycotinine, total NNAL, and total PAHs), we observed no significant difference in the levels ( P = 0.169, P = 0.146, P = 0.171, and P = 0.554, respectively) between smokers of herbal cigarettes and smokers of regular cigarettes. Both total NNAL and total PAHs were significantly correlated with cotinine and trans -3′-Hydroxycotinine ( P < 0.001 for all four correlations). Conclusions: Our findings showed that herbal cigarettes did not deliver less carcinogens than regular cigarettes. The public needs to be aware of this fact, and the Chinese tobacco industry should avoid misleading the public when promoting herbal cigarettes as safer products. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3497–501]
Diaa M. Shakleya - One of the best experts on this subject based on the ideXlab platform.
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simultaneous quantification of nicotine cotinine trans 3 Hydroxycotinine norcotinine and mecamylamine in human urine by liquid chromatography tandem mass spectrometry
Clinica Chimica Acta, 2012Co-Authors: Karl B Scheidweiler, Diaa M. Shakleya, Marilyn A HuestisAbstract:Abstract Background Mecamylamine is a nicotine antagonist under investigation in combination with nicotine replacement for smoking treatment. Methods A simple, rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying nicotine, cotinine, trans-3′-Hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was performed on a Synergi PolarRP column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime. Analytes were monitored by positive mode electrospray ionization and multiple reaction monitoring mass spectrometry. Results Linear dynamic ranges were 1–500 ng/ml for nicotine and norcotinine, 0.5–500 ng/ml for trans-3′-Hydroxycotinine, 0.2–500 ng/ml for cotinine, and 0.1–100 ng/ml for mecamylamine; correlation coefficients were consistently greater than 0.99, and all calibrator concentrations were within 20% of target. Extensive endogenous and exogenous interferences were evaluated. At 3 concentrations spanning the linear dynamic range of the assay, mean extraction efficiencies from urine were 55.1–109.1% with analytical recovery (bias) 82.0–118.7% and total imprecision of 0.7–9.1%. Analytes were stable for 24 h at room temperature, 72 h at 4 °C, 72 h in autosampler at 15 °C and after three freeze/thaw cycles. Conclusion This method is useful for monitoring mecamylamine, nicotine and nicotine metabolites in smoking cessation and other clinical nicotine research.
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Simultaneous quantification of nicotine, cotinine, trans-3'-Hydroxycotinine, norcotinine and mecamylamine in human urine by liquid chromatography-tandem mass spectrometry.
Clinica chimica acta; international journal of clinical chemistry, 2012Co-Authors: Karl B Scheidweiler, Diaa M. Shakleya, Marilyn A HuestisAbstract:Mecamylamine is a nicotine antagonist under investigation in combination with nicotine replacement for smoking treatment. A simple, rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying nicotine, cotinine, trans-3'-Hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was performed on a Synergi PolarRP column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime. Analytes were monitored by positive mode electrospray ionization and multiple reaction monitoring mass spectrometry. Linear dynamic ranges were 1-500 ng/ml for nicotine and norcotinine, 0.5-500 ng/ml for trans-3'-Hydroxycotinine, 0.2-500 ng/ml for cotinine, and 0.1-100 ng/ml for mecamylamine; correlation coefficients were consistently greater than 0.99, and all calibrator concentrations were within 20% of target. Extensive endogenous and exogenous interferences were evaluated. At 3 concentrations spanning the linear dynamic range of the assay, mean extraction efficiencies from urine were 55.1-109.1% with analytical recovery (bias) 82.0-118.7% and total imprecision of 0.7-9.1%. Analytes were stable for 24h at room temperature, 72 h at 4 °C, 72 h in autosampler at 15 °C and after three freeze/thaw cycles. This method is useful for monitoring mecamylamine, nicotine and nicotine metabolites in smoking cessation and other clinical nicotine research. Published by Elsevier B.V.
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Optimization and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, cotinine, trans-3′-Hydroxycotinine and norcotinine in human oral fluid
Analytical and Bioanalytical Chemistry, 2009Co-Authors: Diaa M. Shakleya, Marilyn A HuestisAbstract:An analytical procedure was developed and validated for the simultaneous identification and quantification of nicotine, cotinine, trans -3′-Hydroxycotinine, and norcotinine in 0.5 mL of human oral fluid collected with the Quantisal™ oral fluid collection device. Solid phase extraction and liquid chromatography-tandem mass spectrometry with multiple reaction monitoring were utilized. Endogenous and exogenous interferences were extensively evaluated. Limits of quantification were empirically identified by decreasing analyte concentrations. Linearity was from 1 to 2,000 ng/mL for nicotine and norcotinine, 0.5 to 2,000 ng/mL for trans -3′-Hydroxycotinine, and 0.2 to 2,000 ng/mL for cotinine. Correlation coefficients for calibration curves were >0.99 and analytes quantified within ±13% of target at all calibrator concentrations. Suitable analytical recovery (>91%) was achieved with extraction efficiencies >56% and matrix effects
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simultaneous and sensitive measurement of nicotine cotinine trans 3 Hydroxycotinine and norcotinine in human plasma by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2009Co-Authors: Diaa M. Shakleya, Marilyn A HuestisAbstract:Abstract An LC-MS/MS method for the simultaneous quantification of nicotine, cotinine, trans-3′-Hydroxycotinine and norcotinine in human plasma was developed and fully validated. Potential endogenous and exogenous interferences were extensively evaluated and limits of quantification were determined by decreasing analyte concentration. Analytical ranges were 1–500 ng/mL for nicotine and cotinine, 5–500 ng/mL for trans-3′-Hydroxycotinine and norcotinine. Mean intra- and inter-assay analytical recoveries were between 101.9 and 116.8%, and intra- and inter-assay imprecision were less than 11% RSD for all analytes: parameters were evaluated at three different concentrations across the linear range of the assay. Extraction efficiency was ≥70% for all analytes. This validated method is useful for the determination of nicotine and metabolites in human plasma to support research on the role of nicotine biomarkers on neuronal systems mediating cognitive and affective processes and to differentiate active, passive and environmental exposure.
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optimization and validation of a liquid chromatography tandem mass spectrometry method for the simultaneous quantification of nicotine cotinine trans 3 Hydroxycotinine and norcotinine in human oral fluid
Analytical and Bioanalytical Chemistry, 2009Co-Authors: Diaa M. Shakleya, Marilyn A HuestisAbstract:An analytical procedure was developed and validated for the simultaneous identification and quantification of nicotine, cotinine, trans-3′-Hydroxycotinine, and norcotinine in 0.5 mL of human oral fluid collected with the Quantisal™ oral fluid collection device. Solid phase extraction and liquid chromatography-tandem mass spectrometry with multiple reaction monitoring were utilized. Endogenous and exogenous interferences were extensively evaluated. Limits of quantification were empirically identified by decreasing analyte concentrations. Linearity was from 1 to 2,000 ng/mL for nicotine and norcotinine, 0.5 to 2,000 ng/mL for trans-3′-Hydroxycotinine, and 0.2 to 2,000 ng/mL for cotinine. Correlation coefficients for calibration curves were >0.99 and analytes quantified within ±13% of target at all calibrator concentrations. Suitable analytical recovery (>91%) was achieved with extraction efficiencies >56% and matrix effects <29%. This assay will be applied to the quantification of nicotine and metabolites in oral fluid in a clinical study determining the most appropriate nicotine biomarker concentrations differentiating active, passive, and environmental nicotine exposure.
Peyton Jacob - One of the best experts on this subject based on the ideXlab platform.
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Determination of the Nicotine Metabolites Cotinine and Trans-3′-Hydroxycotinine in Biologic fluids of Smokers and Non-Smokers using Liquid Chromatography - Tandem Mass Spectrometry: Biomarkers for Tobacco Smoke Exposure and for Phenotyping Cytochrome
Journal of Chromatography B, 2011Co-Authors: Peyton Jacob, Lisa Yu, Minjiang Duan, Lita Ramos, Olivia Yturralde, Neal L BenowitzAbstract:Abstract The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3′-Hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography–tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3′-Hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1 ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented.
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determination of the nicotine metabolites cotinine and trans 3 Hydroxycotinine in biologic fluids of smokers and non smokers using liquid chromatography tandem mass spectrometry biomarkers for tobacco smoke exposure and for phenotyping cytochrome p45
Journal of Chromatography B, 2011Co-Authors: Peyton Jacob, Lisa Yu, Minjiang Duan, Lita Ramos, Olivia Yturralde, Neal L BenowitzAbstract:Abstract The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3′-Hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography–tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3′-Hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1 ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented.
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trans 3 Hydroxycotinine disposition kinetics effects and plasma levels during cigarette smoking
British Journal of Clinical Pharmacology, 2008Co-Authors: Neal L Benowitz, Peyton JacobAbstract:Aims (3′R,5′S)-trans-3′-Hydroxycotinine (3-HC) is a major metabolite of nicotine. The aim of this study was to characterize the disposition kinetics of 3-HC in healthy smokers, including metabolism to (3′R,5′S)-trans-3′-Hydroxycotinine glucuronide (3-HC-Gluc). We also studied pharmacologic responses to 3-HC and plasma levels of 3-HC in a group of smokers. Methods Eight cigarette smokers were studied on a clinical research ward. After 5 days of supervised nonsmoking, each subject received an intravenous infusion of 3-HC, 4 µg kg−1 min−1 for 60 min. Plasma and urine levels of 3-HC and 3-HC-Gluc and cardiovascular and subjective responses were examined. Plasma levels of 3-HC, nicotine, and cotinine were measured in 62 smokers on up to three occasions. Results The total plasma clearance of 3-HC averaged 1.3 ml min−1 kg−1, of which 63% was renal excretion of unchanged drug. An average of 29% of the dose was excreted as 3-HC-Gluc. 3-HC did not have nicotine-like cardiovascular effects. Conclusions These findings extend our understanding of the quantitative nature of nicotine metabolism. Such data may be of use in quantitating human exposure to nicotine from tobacco and in studying individual variability in nicotine metabolism.
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Trans‐3′‐Hydroxycotinine: Disposition kinetics, effects and plasma levels during cigarette smoking
British Journal of Clinical Pharmacology, 2008Co-Authors: Neal L Benowitz, Peyton JacobAbstract:Aims (3′R,5′S)-trans-3′-Hydroxycotinine (3-HC) is a major metabolite of nicotine. The aim of this study was to characterize the disposition kinetics of 3-HC in healthy smokers, including metabolism to (3′R,5′S)-trans-3′-Hydroxycotinine glucuronide (3-HC-Gluc). We also studied pharmacologic responses to 3-HC and plasma levels of 3-HC in a group of smokers. Methods Eight cigarette smokers were studied on a clinical research ward. After 5 days of supervised nonsmoking, each subject received an intravenous infusion of 3-HC, 4 µg kg−1 min−1 for 60 min. Plasma and urine levels of 3-HC and 3-HC-Gluc and cardiovascular and subjective responses were examined. Plasma levels of 3-HC, nicotine, and cotinine were measured in 62 smokers on up to three occasions. Results The total plasma clearance of 3-HC averaged 1.3 ml min−1 kg−1, of which 63% was renal excretion of unchanged drug. An average of 29% of the dose was excreted as 3-HC-Gluc. 3-HC did not have nicotine-like cardiovascular effects. Conclusions These findings extend our understanding of the quantitative nature of nicotine metabolism. Such data may be of use in quantitating human exposure to nicotine from tobacco and in studying individual variability in nicotine metabolism.
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Nicotine metabolism and elimination kinetics in newborns.
Clinical Pharmacology & Therapeutics, 2000Co-Authors: Delia A. Dempsey, Peyton Jacob, Neal L BenowitzAbstract:Objective To characterize the presence of and elimination kinetics of nicotine and its metabolites in newborns. Methods Blood samples from 13 newborns were collected during the first day of life and analyzed for nicotine and cotinine. Single daily urine samples were collected from nine newborns for up to 7 days and analyzed by gas chromatography–mass spectrometry for nicotine, cotinine, 3′–Hydroxycotinine, and their conjugates. NONMEM was used to determine population half-life values. Results Blood and urine data gave similar results for nicotine and cotinine elimination kinetics. The elimination half-life for nicotine was 11.2 hours (95% confidence interval [CI], 8.0 to 18.9) based on blood data and 9.0 hours (95% CI, 7.0 to 12.4) based on urine data. The elimination half-life for cotinine was 16.3 hours (95% CI, 12.4 to 23.9) based on blood data and was 22.8 hours (95% CI, 19.5 to 25.8) based on urine data. The elimination half-lives for the other metabolites were 13 hours for conjugated nicotine; 19.8 hours for conjugated cotinine; 18.8 hours for 3′–Hydroxycotinine; and 19.4 hours for conjugated 3′–Hydroxycotinine. The half-life of nicotine is three to four times longer in newborns than in adults, whereas the half-life of cotinine is similar in newborns and adults. Conclusions In adults, CYP2A6 is the predominant enzyme responsible for the metabolism of both nicotine and cotinine. The prolonged elimination of nicotine but not of cotinine in the newborn compared with that in the adult may be a result of different newborn CYP2A6 enzymatic substrate specificity, low CYP2A6 activity with another enzyme that is primarily responsible for cotinine metabolism, or differences in tissue distribution. Clinical Pharmacology & Therapeutics (2000) 67, 458–465; doi: 10.1067/mcp.2000.106129
Hayden Mcrobbie - One of the best experts on this subject based on the ideXlab platform.
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Systematic review of the relationship between the 3-Hydroxycotinine/cotinine ratio and cigarette dependence
Psychopharmacology, 2011Co-Authors: Oliver West, Peter Hajek, Hayden McrobbieAbstract:Rationale Individual differences in the rate of nicotine metabolism (RNM) could be related to dependence and success in stopping smoking. A range of studies have examined RNM measured by the ratio of trans -3′-Hydroxycotinine and cotinine in body fluids (the ratio). A systematic review of this literature is needed to draw conclusions and identify gaps in evidence. Objective The aim of this study is to review evidence on the association of the ratio to cigarette dependence and its role in individual tailoring of smoking cessation pharmacotherapy. Results We reviewed 27 studies of the ratio related to its reliability, validity, and relationship to dependence. The ratio is a reasonably accurate proxy for RNM. There is little evidence that the ratio is related to questionnaire measures of dependence, though the existing data are limited and the ratio has been linked to smoking at night and to some aspects of smoking topography. The ratio is also only weakly associated with cigarette consumption. Its relationship to the severity of withdrawal symptoms seems also weak at best, but limited data exist. One study suggests the ratio predicts outcome of unaided quitting. Importantly, the ratio seems to predict responses both to NRT and bupropion, and thus could guide pharmacotherapy. Conclusions The evidence that the ratio is related to smoking behaviours and to cigarette dependence is limited, but the ratio seems to influence treatment response to two stop smoking medications. Further studies of the relationship between the ratio and cigarette dependence and trials of ratio-guided pharmacotherapy are needed.
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systematic review of the relationship between the 3 Hydroxycotinine cotinine ratio and cigarette dependence
Psychopharmacology, 2011Co-Authors: Oliver West, Peter Hajek, Hayden McrobbieAbstract:Rationale Individual differences in the rate of nicotine metabolism (RNM) could be related to dependence and success in stopping smoking. A range of studies have examined RNM measured by the ratio of trans-3′-Hydroxycotinine and cotinine in body fluids (the ratio). A systematic review of this literature is needed to draw conclusions and identify gaps in evidence.
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Systematic review of the relationship between the 3-Hydroxycotinine/cotinine ratio and cigarette dependence
Psychopharmacology, 2011Co-Authors: Oliver West, Peter Hajek, Hayden McrobbieAbstract:Rationale Individual differences in the rate of nicotine metabolism (RNM) could be related to dependence and success in stopping smoking. A range of studies have examined RNM measured by the ratio of trans-3′-Hydroxycotinine and cotinine in body fluids (the ratio). A systematic review of this literature is needed to draw conclusions and identify gaps in evidence.
