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Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.

  • Prenatal Tobacco Exposure, Biomarkers for Tobacco in Meconium, and Neonatal Growth Outcomes
    The Journal of pediatrics, 2012
    Co-Authors: Sarah K. Himes, Karl B. Scheidweiler, Laura R. Stroud, Raymond Niaura, Marilyn A Huestis
    Abstract:

    Objective To assess relationships between marker concentrations of tobacco in meconium and weekly self-reported maternal cigarette consumption, and prediction of neonatal growth outcomes. Study design Pregnant mothers (n = 119) from a longitudinal maternal smoking and infant neurobehavioral study (Behavior and Mood in Babies and Mothers [BAM BAM]) provided daily tobacco smoking histories. Nicotine, cotinine, and trans -3′-hydroxycotinine concentrations were quantified in 111 neonatal meconium specimens by liquid chromatography-tandem mass spectrometry. Results Median self-reported third trimester smoking was 5.9 cigarettes per day among smokers. Meconium samples from infants born to non-smokers (n = 42) were negative for tobacco markers, while specimens from self-reported smokers (n = 41) were positive for (median, range) nicotine (50.1 ng/g, 3.9-294), cotinine (73.9 ng/g, 6.4-329), and trans -3′-hydroxycotinine (124.5 ng/g, 10.2-478). Quitters (n = 28) self-reported stopping smoking at gestational weeks 2-39. Four meconium specimens from quitters were positive for tobacco biomarkers. Reduced birth weight, length, and head circumference significantly correlated with presence of meconium markers but not with individual or total marker concentrations. Among quitters and smokers, reduced infant birth weight, head circumference, and gestational age correlated with total and average daily cigarette consumption in the second and third trimesters. Conclusion Smoking cessation or reduction during pregnancy improved neonatal outcomes. The window of detection for tobacco in meconium appears to be the third trimester; however, low exposure in this trimester failed to be detected. These results will aid physicians in educating women who are pregnant or thinking about becoming pregnant on the negative consequences of smoking during pregnancy. In addition, infants at risk can be identified at birth to assist early intervention efforts.

  • simultaneous quantification of nicotine cotinine trans 3 hydroxycotinine norcotinine and mecamylamine in human urine by liquid chromatography tandem mass spectrometry
    Clinica Chimica Acta, 2012
    Co-Authors: Karl B. Scheidweiler, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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.

  • 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, 2012
    Co-Authors: Karl B. Scheidweiler, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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.

  • Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2011
    Co-Authors: Marta Concheiro, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were

  • nicotine and metabolites in meconium as evidence of maternal cigarette smoking during pregnancy and predictors of neonatal growth deficits
    Nicotine & Tobacco Research, 2010
    Co-Authors: Teresa R Gray, Rina Das Eiden, Kenneth E Leonard, Gerard J Connors, Shannon Shisler, Marilyn A Huestis
    Abstract:

    Introduction: Many women continue tobacco use during preg- nancy despite known adverse consequences on neonatal growth and development. Testing meconium, the first neonatal feces, for tobacco biomarkers offers objective evidence of prenatal tobacco exposure. However, relationships between the amount, frequency, and timing of cigarette smoking during gestation and tobacco biomarker meconium concentrations and neonatal outcomes are unclear. Methods: Eighty-seven pregnant women provided detailed self-reports of daily tobacco consumption throughout pregnancy. Nicotine, cotinine, and trans-3-hydroxycotinine were quanti- fied in neonatal meconium by liquid chromatography-tandem mass spectrometry. Results: Among nonsmokers, all meconium specimens were negative, whereas nearly all meconium specimens were positive if the mother self-reported tobacco use into the third trimester. Tobacco biomarker concentrations were significantly albeit weakly correlated with mean cigarettes per day in the third trimester. Reduced birth weight, gestational age, or head cir- cumference were observed if meconium contained one or more tobacco biomarkers, but deficits did not correlate with bio - marker concentrations. Conclusion: While previously thought to reflect second and third trimester drug exposure, meconium appears to reliably identify only third trimester drug use. While a 10 ng/g nicotine, cotinine, or trans-3-hydroxycotinine cutoff in meconium was previously proposed to differentiate tobacco-exposed from nonexposed or passively exposed neonates, improved maternal self-reporting techniques in this cohort suggest that a lower cutoff, equivalent to the analytic limits of quantification, is more appropriate.

Simona Pichini - One of the best experts on this subject based on the ideXlab platform.

  • Successful Nicotine Intake in Medical Assisted Use of E-Cigarettes: A Pilot Study.
    International journal of environmental research and public health, 2015
    Co-Authors: Roberta Pacifici, Manuela Pellegrini, Simona Pichini, Silvia Graziano, Giuseppina Massaro, Fabio Beatrice
    Abstract:

    The electronic cigarette (e-cig) has gained popularity as an aid in smoking cessation programs mainly because it maintains the gestures and rituals of tobacco smoking. However, it has been shown in inexperienced e-cig users that ineffective nicotine delivery can cause tobacco craving that could be responsible for unsuccessful smoking reduction/cessation. Moreover, the incorrect use of an e-cig could also led to potential nicotine overdosage and intoxication. Medically assisted training on the proper use of an e-cig plus behavioral support for tobacco dependence could be a pivotal step in avoiding both issues. We performed an eight-month pilot study of adult smokers who started e-cig use after receiving a multi-component medically assisted training program with monitoring of nicotine intake as a biomarker of correct e-cig use. Participants were tested during follow-up for breath carbon monoxide (CO), plasma cotinine and trans-3’-hydroxycotinine, and number of tobacco cigarettes smoked. At the end of the first, fourth, and eighth month of follow-up, 91.1, 73.5, and 76.5% of participants respectively were e-cig users (‘only e-cig’ and ‘dual users’). They showed no significant variation in plasma cotinine and trans-3’-hydroxycotinine with respect to the start of the study when they smoked only tobacco cigarettes, but a significant reduction in breath CO. The proposed medically assisted training program of e-cig use led to a successful nicotine intake, lack of typical cigarette craving and overdosage symptoms and a significant decrease in the biomarker of cigarette combustion products.

  • Liquid chromatography/electrospray ionization tandem mass spectrometry assay for determination of nicotine and metabolites, caffeine and arecoline in breast milk.
    Rapid Communications in Mass Spectrometry, 2007
    Co-Authors: Manuela Pellegrini, Abhilasha Durgbanshi, Emilia Marchei, Federica Vagnarelli, Oscar Garcia-algar, Oriol Vall, Silvia Rossi, Simona Pichini
    Abstract:

    A procedure based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) is described for the determination of nicotine and its principal metabolites cotinine, Trans-3-Hydroxycotinine and cotinine-N-oxide, caffeine and arecoline in breast milk, using N-ethylnorcotinine as internal standard.Liquid/liquid extractionwithchloroform/isopropanol (95:5,v/v)was used fornicotine,cotinine, Trans-3-Hydroxycotinine, cotinine-N-oxide and caffeine under neutral conditions and for arecoline under basic conditions. Chromatography was performed on a C8 reversed-phase column using a gradient of 50mM ammonium formate, pH 5.0, and acetonitrile as a mobile phase at a flow rate of 0.5mL/min. Separated analytes were determined by electrospray ionization tandem mass spectrometry in the positive ion mode using multiple reaction monitoring. Limits of quantification were 5 mg/L for nicotine, cotinine, Trans-3-Hydroxycotinine, cotinine-N-oxide and caffeine, and 50 mg/L for arecolineusing1mLhumanmilkperassay.Calibrationcurveswerelinearoverthecalibration ranges for all the substances under investigation, with a minimum r 2 >0.998. At three concentrations spanning the linear dynamic range of the assay, mean recoveries from breast milk ranged between 71.8 and 77.4% for different analytes. This method was applied to the analysis of analytes in human milk to assess substance exposure in breast-fed infants in relation to eventual clinical outcomes. This LC/MS/MS assay provides adequate sensitivity and performance characteristics for the simultaneous quantification of biomarkers of three of the drugs most commonly used worldwide (tobacco, caffeine and areca nut). Copyright # 2007 John Wiley & Sons, Ltd.

  • Liquid chromatography/electrospray ionization tandem mass spectrometry assay for determination of nicotine and metabolites, caffeine and arecoline in breast milk.
    Rapid communications in mass spectrometry : RCM, 2007
    Co-Authors: Manuela Pellegrini, Abhilasha Durgbanshi, Emilia Marchei, Federica Vagnarelli, Oscar Garcia-algar, Oriol Vall, Silvia Rossi, Simona Pichini
    Abstract:

    A procedure based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) is described for the determination of nicotine and its principal metabolites cotinine, Trans-3-Hydroxycotinine and cotinine-N-oxide, caffeine and arecoline in breast milk, using N-ethylnorcotinine as internal standard. Liquid/liquid extraction with chloroform/isopropanol (95:5, v/v) was used for nicotine, cotinine, Trans-3-Hydroxycotinine, cotinine-N-oxide and caffeine under neutral conditions and for arecoline under basic conditions. Chromatography was performed on a C(8) reversed-phase column using a gradient of 50 mM ammonium formate, pH 5.0, and acetonitrile as a mobile phase at a flow rate of 0.5 mL/min. Separated analytes were determined by electrospray ionization tandem mass spectrometry in the positive ion mode using multiple reaction monitoring. Limits of quantification were 5 microg/L for nicotine, cotinine, Trans-3-Hydroxycotinine, cotinine-N-oxide and caffeine, and 50 microg/L for arecoline using 1 mL human milk per assay. Calibration curves were linear over the calibration ranges for all the substances under investigation, with a minimum r(2) > 0.998. At three concentrations spanning the linear dynamic range of the assay, mean recoveries from breast milk ranged between 71.8 and 77.4% for different analytes. This method was applied to the analysis of analytes in human milk to assess substance exposure in breast-fed infants in relation to eventual clinical outcomes. This LC/MS/MS assay provides adequate sensitivity and performance characteristics for the simultaneous quantification of biomarkers of three of the drugs most commonly used worldwide (tobacco, caffeine and areca nut).

  • Solid-phase extraction of nicotine and its metabolites for high-performance liquid chromatographic determination in urine.
    Journal of chromatography. B Biomedical applications, 1995
    Co-Authors: Piergiorgio Zuccaro, Mirella Rosa, A.r. Passa, Ilaria Altieri, Simona Pichini, Roberta Pacifici
    Abstract:

    Abstract A solid-phase extraction, using Extrelut-1 glass columns, has been applied to urine samples of both passive and active smokers for high-performance liquid chromatographic determination of nicotine and its metabolites cotinine and trans -3′-hydroxycotinine. Chromatography was performed using a reversed-phase LC 8 DB column and a mobile phase consisting of wateracetonitrile (80:9, v/v) containing 5 ml triethylamine, 670 mg/l sodium heptanesulphonate, and 0.034 M each of K 2 HPO 4 and citric acid (pH 4.4), at a flow-rate of 1.6 ml/min. The results obtained indicate that solid-phase extraction is a reliable and quick procedure which can be applied also to other nicotine metabolites.

  • Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection
    Journal of Chromatography B: Biomedical Sciences and Applications, 1993
    Co-Authors: Piergiorgio Zuccaro, Mirella Rosa, A.r. Passa, G. Ricciarello, Ilaria Altieri, Simona Pichini, Roberta Pacifici
    Abstract:

    Abstract A simple and reliable reversed-phase high-performance liquid chromatographic method with ultraviolet detection is described for the quantitation of nicotine and its metabolites cotinine, trans-3′-hydroxycotinine, norcotinine and cotinine N-oxide in human serum. The analytes and the internal standard, N-ethylnorcotinine, were extracted by solid-phase extraction before chromatography. Two different columns and mobile phases with gradient systems were used. The detection limit of the assay was 10 ng/ml for nicotine, 3 ng/ml for cotinine N-oxide and 5 ng/ml for cotinine, trans-3′-hydroxycotinine and norcotinine. The concentrations of nicotine and its metabolites in the serum of 12 cigarette smokers are reported.

Neal L. Benowitz - One of the best experts on this subject based on the ideXlab platform.

  • Slower nicotine metabolism among postmenopausal Polish smokers
    Pharmacological Reports, 2018
    Co-Authors: Leon Kosmider, Neal L. Benowitz, Marcin Delijewski, Bartosz Koszowski, Andrzej Sobczak, Maciej L. Goniewicz
    Abstract:

    Background A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine — trans -3′-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. Methods In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6 ± 13.0), we collected spot urine samples and measured trans -3′-hydroxycotinine (3-HC) and cotinine levels with LC–MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. Results In the whole study group, an average NMR was 4.8 (IQR 3.4–7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1–8.8 vs . 4.3; IQR 2.8–6.4). No differences were found among group ages of male smokers. Conclusions This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment.

  • Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries.
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2016
    Co-Authors: James W. Baurley, Neal L. Benowitz, Christopher K. Edlund, Carissa I. Pardamean, David V. Conti, Ruth E. Krasnow, Harold S. Javitz, Hyman Hops, Gary E. Swan, Andrew W. Bergen
    Abstract:

    Introduction: Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3′-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed.

  • variation in trans 3 hydroxycotinine glucuronidation does not alter the nicotine metabolite ratio or nicotine intake
    PLOS ONE, 2013
    Co-Authors: Qian Zhou, Jasjit S Ahluwalia, Neal L. Benowitz, Rachel F Tyndale
    Abstract:

    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.

  • Stability of the Nicotine Metabolite Ratio in Smokers of Progressively Reduced Nicotine Content Cigarettes
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2013
    Co-Authors: Gideon St. Helen, Peyton Jacob, Neal L. Benowitz
    Abstract:

    Introduction: The nicotine metabolite ratio (NMR), the ratio of trans-3′-hydroxycotinine (3-HC) to cotinine, has been used as a biomarker of the rate of CYP2A6-mediated nicotine metabolism. While stable in smokers who maintain constant smoking consumption, since smoking has been shown to inhibit nicotine metabolism and this inhibition could be mediated by the nicotine in the smoke, NMR could change during nicotine reduction. The objective of this study was to determine the reproducibility (or stability) of plasma NMR in smokers of progressively reduced nicotine content (RNC) cigarettes.

  • 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, 2011
    Co-Authors: Peyton Jacob, Minjiang Duan, Lita Ramos, Olivia Yturralde, Lisa Yu, Neal L. Benowitz
    Abstract:

    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.

Peyton Jacob - One of the best experts on this subject based on the ideXlab platform.

  • Stability of the Nicotine Metabolite Ratio in Smokers of Progressively Reduced Nicotine Content Cigarettes
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2013
    Co-Authors: Gideon St. Helen, Peyton Jacob, Neal L. Benowitz
    Abstract:

    Introduction: The nicotine metabolite ratio (NMR), the ratio of trans-3′-hydroxycotinine (3-HC) to cotinine, has been used as a biomarker of the rate of CYP2A6-mediated nicotine metabolism. While stable in smokers who maintain constant smoking consumption, since smoking has been shown to inhibit nicotine metabolism and this inhibition could be mediated by the nicotine in the smoke, NMR could change during nicotine reduction. The objective of this study was to determine the reproducibility (or stability) of plasma NMR in smokers of progressively reduced nicotine content (RNC) cigarettes.

  • 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, 2011
    Co-Authors: Peyton Jacob, Minjiang Duan, Lita Ramos, Olivia Yturralde, Lisa Yu, Neal L. Benowitz
    Abstract:

    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.

  • 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, 2011
    Co-Authors: Peyton Jacob, Minjiang Duan, Lita Ramos, Olivia Yturralde, Lisa Yu, Neal L. Benowitz
    Abstract:

    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.

  • trans 3 hydroxycotinine disposition kinetics effects and plasma levels during cigarette smoking
    British Journal of Clinical Pharmacology, 2008
    Co-Authors: Neal L. Benowitz, Peyton Jacob
    Abstract:

    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.

  • Trans‐3′‐hydroxycotinine: Disposition kinetics, effects and plasma levels during cigarette smoking
    British Journal of Clinical Pharmacology, 2008
    Co-Authors: Neal L. Benowitz, Peyton Jacob
    Abstract:

    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.

Diaa M. Shakleya - One of the best experts on this subject based on the ideXlab platform.

  • simultaneous quantification of nicotine cotinine trans 3 hydroxycotinine norcotinine and mecamylamine in human urine by liquid chromatography tandem mass spectrometry
    Clinica Chimica Acta, 2012
    Co-Authors: Karl B. Scheidweiler, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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.

  • 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, 2012
    Co-Authors: Karl B. Scheidweiler, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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.

  • Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2011
    Co-Authors: Marta Concheiro, Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were

  • 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, 2009
    Co-Authors: Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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

  • 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, 2009
    Co-Authors: Diaa M. Shakleya, Marilyn A Huestis
    Abstract:

    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.