Development of a method for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine of nonsmokers and smokers using liquid chromatography/tandem mass spectrometry.

摘要

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an efficient biomarker of tobacco-specific carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The ability to monitor biomarker concentrations is very important in understanding potential cancer risk. An analytical method using molecularly imprinted polymer (MIP) column coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) for the determination of total NNAL in human urine was developed and validated. The combination of MIP column extraction and LC-MS/MS can provide a high sensitive and relatively simple analytical method. The limit of detection (LOD) was 0.30 pg/ml and analysis time was 6min. The method has been applied to urine samples of 36 nonsmokers and 207 smokers. NNAL was found to be significantly higher in the urine of smokers compared with nonsmokers. Compared with smokers with blended cigarettes, Chinese virginia cigarettes smokers had low urinary NNAL levels. There was a direct association between the 24-h mouth-level exposure of carcinogen NNK from cigarette smoking and the concentration of NNAL in the urine of smokers. However, there was not a positive correlation between urinary total NNAL levels in 24 h and tar. Total urinary NNAL is a valuable biomarker for monitoring exposure to carcinogenic NNK in smokers and in nonsmokers. A prediction model of cigarette smoke NNK and urinary average NNAL levels in 24 h was established (y=2.8987x-245.38, r2=0.9952, n=204).