Combined analysis of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in urine by heart cutting two‐dimensional LC‐MS/MS

Abstract

Abstract4‐(Methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine are valuable biomarkers of tobacco smoke exposure. It is crucial to detect them for evaluating the health impact of exposure and the understanding of detoxification mechanism in humans. Considering the huge difference concentration in smoker's urine, they are always detected separately rather than simultaneously. In this work, we have developed an effective system of two‐dimensional liquid chromatography coupled with tandem mass spectrometry for high‐throughput simultaneous determination of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in smoker's urine. The strong cation‐exchange and the reversed‐phase chromatography were chosen as the first and second dimensional studies. The orthogonality of this two‐dimensional system was evaluated through the separation of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine. Compared with traditional methodologies, the limits of detection of the method were 0.24 pg/mL and 0.054 ng/mL for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine respectively. The recoveries of the spiked samples were 99.8‐105.1 and 111.9‐114.2% for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine respectively in urine. The precisions of the method were 0.43‐3.07 and 0.73‐2.11%. The method is useful for monitoring 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and cotinine in smoking and satisfying to evaluate the tobacco exposure.