title: Enhanced nicotine metabolism in HIV-1-positive smokers compared with HIV-negative smokers: simultaneous determination of nicotine and its four metabolites in their plasma using a simple and sensitive electrospray ionization liquid chromatography-tandem mass spectrometry technique.
abstract: Smoking is approximately three times more prevalent in HIV-1-positive than HIV-negative individuals in the United States. Nicotine, which is the major constituent of tobacco, is rapidly metabolized mainly by cytochrome P450 (CYP2A6) to many metabolites. In this study, we developed a simple, fast, and sensitive electrospray ionization liquid chromatography-tandem mass spectrometry method using a strong cation solid phase extraction, and determined the concentration of nicotine and its four major metabolites (cotinine, nornicotine, norcotinine, and trans-3'-hydroxycotinine) in the plasma of HIV-1-positive and HIV-negative smokers. The multiple reaction monitoring transitions for nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine, norcotinine, nicotine-d4, and cotinine-d3 were selected at mass-to-charge ratios of 163.3/117.1, 177.5/80.3, 193.2/80.1, 149.5/132.3, 163.4/80.3, 167.3/121.4, and 180.3/101.2, respectively. The lower limit of quantitation for nicotine and its metabolites was 0.53 ng/ml, which is relatively more sensitive than those previously reported. The concentration of nicotine was detected 5-fold lower in HIV-1-positive smokers (7.17 ± 3.8 ng/ml) than that observed in HIV-negative smokers (33.29 ± 15.4 ng/ml), whereas the concentration of the metabolite nornicotine was 3-fold higher in HIV-1-positive smokers (6.8 ± 2.9 ng/ml) than in HIV-negative smokers (2.3 ± 1.2 ng/ml). Although it was statistically nonsignificant, the concentration of the metabolite cotinine was also higher in HIV-1-positive smokers (85.6 ± 60.5 ng/ml) than in HIV-negative smokers (74.9 ± 40.5 ng/ml). In conclusion, a decrease in the concentration of nicotine and an increase in the concentration of its metabolites in HIV-1-positive smokers compared with HIV-negative smokers support the hypothesis that nicotine metabolism is enhanced in HIV-1-positive smokers compared with HIV-negative smokers.
authors.affiliation: School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.A., A.K., S.K.); and Department of Oral and Craniofacial Science, School of Dentistry, University of Missouri-Kansas City, Kansas City, Missouri (C.M.).
authors.forename: Ravinder
authors.initials: R
authors.lastname: Earla
authors.forename: Anusha
authors.initials: A
authors.lastname: Ande
authors.forename: Carole
authors.initials: C
authors.lastname: McArthur
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000328:Adult; D001711:Biotransformation; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000097:blood*; D015203:Reproducibility of Results; D012907:Smoking / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D018722:Nicotinic Agonists; C066333:norcotinine; C001381:hydroxycotinine; D009538:Nicotine; C005311:nornicotine; D003367:Cotinine