An LC-MS/MS method for the quantification of tobacco-specific carcinogen protein adducts.

4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its major metabolite 4-(methylnitrosamino)-l-(3-pyri-dine)-l-butanol (NNAL) are tobacco-specific lung carcinogens. Methods have been developed to quantify NNK- and NNAL-specific DNA adducts in pre-clinical samples but are less feasible to translation due to limited access to target tissues for sufficient DNA. NNAL-specific DNA or protein adducts have never been detected in clinical samples, which are critical to support the physiological relevance of NNAL bioactivation and carcinogenesis. We reported a sensitive and specific LC-MS/MS method to quantify hydrolyzed NNAL adduct, 1-(3-pyridinyl)-1,4-butanediol (PBD). The method was applicable to variety of biological samples, to assess tobacco exposure and estimate NNAL bioactivation.