Nicotine, cotinine and trans-3'-hydroxycotinine (3HC)/cotinine ratios were determined by tandem mass spectrometry (LC/MS/MS) employing stable isotope (deuterated) labeled internal standards as we have previously reported (47) and similar to that reported by others (48). Nicotine and cotinine were determined to compare baseline nicotine exposure between the three genotypes, and 3HC/cotinine ratios were determined to control for possible differences in the rate of nicotine clearance (48).