Cotinine and trans 3′-hydroxycotinine in dried blood spots as biomarkers of tobacco exposure and nicotine metabolism

Tobacco use is the major preventable cause of premature death in the United States. Second-hand smoke (SHS) exposure also contributes to a number of premature deaths as well as other negative health outcomes. An accurate assessment of tobacco smoke exposure is critical to understanding these disease processes. The plasma concentration of cotinine, the primary metabolite of nicotine, is widely accepted as a quantitative measure of tobacco and SHS exposure. However, it is not always feasible to collect plasma. Dried blood spots (DBS), which are collected routinely from newborns and often from young children for lead screening, provide an alternative sampling method. We have developed a quantitative high throughput liquid chromatography tandem mass spectrometry method for the analysis of cotinine in DBS. The limit of quantitation was 0.3 ng/g (∼ 0.2 ng/ml plasma). Cotinine levels in DBS from 83 smokers and 99 non-smokers exposed to SHS were determined. Plasma cotinine concentrations in these subjects ranged from