Development of a heart-cutting supercritical fluid chromatography-high-performance liquid chromatography coupled to tandem mass spectrometry for the determination of four tobacco-specific nitrosamines in mainstream smoke.

This paper proposed a newly developed heart-cutting two-dimensional supercritical fluid chromatography-high-performance liquid chromatography system coupled to tandem mass spectrometry (SFC-HPLC-MS/MS) for the determination of four tobacco-specific nitrosamines (TSNAs) in cigarette mainstream smoke. The orthogonality of five SFC columns and two HPLC columns was evaluated. The 1-AA column was applied for the first dimensional (1D) SFC separation to isolate the target compounds from the complex cigarette smoke matrices, and a trapping column in conjunction with an isocratic pump was employed to capture the 1D elutes. Then, the trapped 1D elutes were transferred into the C18 column through a two-position/six-port valve for the second dimensional (2D) analysis. The ion suppression was significantly reduced by the established SFC-HPLC system; meanwhile, the matrix interferences were eliminated as the results demonstrated. A dynamic range between 0.1 and 20 ng/mL was achieved with LOQs of 0.72 μg/cig for N-nitrosonornicotine (NNN), 0.66 μg/cig for nicotine-derived nitrosamine ketone (NNK), 0.81 μg/cig for N-nitrosoanatabine (NAT), and 0.39 μg/cig for N-nitrosoanabasine (NAB). All the results revealed that the presented method exhibited good repeatabilities and recoveries and could be used as a rapid and reliable approach for routine analysis of TSNAs in mainstream smoke.