Quantitative method for analysis of tobacco-specific N-nitrosamines in mainstream cigarette smoke by using heart-cutting two-dimensional liquid chromatography with tandem mass spectrometry.

A heart-cutting two dimensional liquid chromatography coupled with tandem mass spectrometry method was developed for the analysis of tobacco-specific N-nitrosamines (TSNAs) at low concentration level in Virginia-type cigarette smoke. A strong cation exchange column was utilized for the first dimensional separation, which effectively removed acidic and neutral components in the smoke, followed by a reversed phase liquid chromatography coupled with tandem mass spectrometric analysis. To capture components of the TSNAs in the effluent on the trapping column, a compensating pump was applied for online dilution and pH adjustment during the period of the TSNAs fraction transferring and enrichment. Highly sensitive determination of the TSNAs in mainstream cigarette smoke was achieved by isotope deuterated internal standards under the multiple reaction monitoring mode. Compared with traditional methodologies, the method was almost no matrix interference. Limits of quantity for the TSNAs were within 0.027-0.094 ng/mL, and the results showed good reproducibility and accuracy. Finally, the new method was applied for analysis of the Kentucky reference cigarettes and the results agreed well with joint experiments of Cooperation Centre for Scientific Research Relative to Tobacco.