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.
Footnotes
- Received September 30, 2013.
- Accepted December 3, 2013.
This research was supported by the National Institutes of Health National Institute on Drug Abuse [Grant R21 DA031616] and the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant R01 AA022063].
↵This article has supplemental material available at dmd.aspetjournals.org.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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