Abstract
Introduction: Based on previous metabolism studies carried out in patas monkeys, we hypothesized that urinary 3'-hydroxynorcotinine could be a specific biomarker for uptake and metabolism of the carcinogen N'-nitrosonornicotine in people who use tobacco products. Methods: We developed a method for quantitation of 3'-hydroxynorcotinine in human urine. [Pyrrolidinone-13C4]3'-hydroxynorcotinine was added to urine as an internal standard, the samples were treated with β-glucuronidase, partially purified by solid supported liquid extraction and quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. Results: The method was accurate (average accuracy = 102%) and precise (coefficient of variation = 5.6%) in the range of measurement. 3'-Hydroxynorcotinine was detected in 48 urine samples from smokers (mean 393±287 pmol/ml urine) and 12 samples from individuals who had stopped smoking and were using the nicotine patch (mean 658±491 pmol/ml urine), but not in any of 10 samples from nonsmokers. Conclusions: Since the amounts of 3'-hydroxynorcotinine found in smokers' urine were approximately 50 times greater than the anticipated daily dose of N'-nitrosonornicotine, we concluded that it is a metabolite of nicotine or one of its metabolites, comprising perhaps 1% of nicotine intake in smokers. Therefore, it would not be suitable as a specific biomarker for uptake and metabolism of N'-nitrosonornicotine. Since 3'-hydroxynorcotinine has never been previously reported as a constituent of human urine, further studies are required to determine its source and mode of formation.
Original language | English (US) |
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Pages (from-to) | 524-529 |
Number of pages | 6 |
Journal | Nicotine and Tobacco Research |
Volume | 17 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2015 |
Bibliographical note
Publisher Copyright:© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.