Development of a method for the determination of 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone in dust using liquld chromatography tandem mass spectrometry

Abstract

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific nitrosamine found only intobacco products. The ability to monitor biomarker concentrations is very important in understanding environmentaltobacco smoke (ETS). In this study, an efficient and sensitive method for the analysis of NNK in dust wasdeveloped and validated using liquid chromatography tandem mass spectrometry. Dust was collected with filterpaper soaked in methanol. The standard solution and dust sample were diluted with 100 mM ammonium acetateand extracted using dichloromethane. Our calibration curves ranged from 25 to 104 pg/mL. Excellent linearitywas obtained with correlation coefficient values between 0.9996 and 1.0000. The limit of detection (LOD) was5 pg/mL (S/N ≥ 3) and the retention time was 10 min. The limit of quantification (LOQ) was 25 pg/mL, andthe acceptance criteria was the rate of 98-103% (80-120% at levels up to 3×LOQ). The coefficient of variations(CV) was 2.8%. Accuracies determined from dust samples spiked with four different levels of NNK racurvesranged that from 25 to 104 pg/mL. Excellent linearity was obtained between 92.1% and 114%. The precisionof the method was acceptable (5% of CV). The recovery rates of the whole analytical procedure at low, medium,and high levels were 105.7-116.5% for NNK. The carry-over effects during LC-MS/MS analysis were notobserved for NNK. This manuscript summarizes the scientific evidence on the use of markers to measure ETS.