Nicotine exposure and metabolizer phenotypes from analysis of urinary nicotine & its 15 metabolites by LC–MS

Smokers who inhale less deeply are exposed to lower amounts of the toxic substances present in tobacco smoke. In order to more rigorously assess tobacco smoke exposure, it is necessary to have an accurate method for quantifying nicotine and all of its known metabolites. Methods: A stable-isotope dilution LC–MRM/MS assay has been developed for quantification of urinary nicotine and the 15 possible metabolites that could arise from known metabolic pathways. Nicotine, cotinine, trans-3´-hydroxy-cotinine, nicotine-N-oxide, cotinine-N-oxide, nornicotine, norcotinine and 4-hydroxy-4-(3-pyridyl)butanoic acid were quantified by direct analysis. The corresponding glucuronide metabolites were quantified after urine hydrolysis with β-glucuronidase. Results: Nicotine and all...