title: 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 P450 2A6 activity.
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 0.1ng/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.
authors.affiliation: Department of Medicine, San Francisco General Hospital Medical Center, 1001 Potrero Avenue, University of California, San Francisco, UCSF Box 1220, San Francisco, CA 94143-1220, USA. peyton.jacob@ucsf.edu
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Lisa
authors.initials: L
authors.lastname: Yu
authors.forename: Minjiang
authors.initials: M
authors.lastname: Duan
authors.forename: Lita
authors.initials: L
authors.lastname: Ramos
authors.forename: Olivia
authors.initials: O
authors.lastname: Yturralde
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods*; D003367:Cotinine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D065637:Cytochrome P-450 CYP2A6; D006801:Humans; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012907:Smoking / Q000097:blood / Q000378:metabolism* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods; D014028:Tobacco Smoke Pollution / Q000032:analysis*
chemical_list: D015415:Biomarkers; D014028:Tobacco Smoke Pollution; C001381:hydroxycotinine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine