Estimation of nicotine dose after low-level exposure using plasma and urine nicotine metabolites

Abstract

Background: We sought to determine the optimal plasma and urine nicotine metabolites, alone or in combination, to estimate the systemic dose of nicotine after low-level exposure. Methods: We dosed 36 nonsmokers with 100, 200, or 400 μg p.o. of deuterium-labeled nicotine (doses similar to exposure to secondhand smoke) daily for 5 days and then measured plasma and urine nicotine metabolites at various intervals over 24 hours. Results: The strongest correlations with nicotine dose were seen for the sum of four (cotinine + cotinineglucuronide + trans-3′-hydroxycotinine + 3HC-glucuronide) or six (including also nicotine + nicotineglucuronide) of the major nicotine metabolites in 24-hour urine collection (r = 0.96), with lesser correlations for these metabolites using spot urines corrected for creatinine at various times of day (r = 0.72-0.80). The sum of plasma cotinine + trans-3′- hydroxycotine was more highly correlated with nicotine dose than plasma cotinine alone (r = 0.82 versus 0.75). Conclusions: Our results provide guidance for the selection of biomarkers to estimate the dose of nicotine taken in low-level (secondhand smoke) tobacco exposure. Impact: This is probably relevant to active smoking as well. ©2010 AACR.