Analysis of Traces of Tobacco-Specific Nitrosamines (TSNAs) in USP Grade Nicotine, E-Liquids, and Particulate Phase Generated by the Electronic Smoking Devices

The present study describes the development of a liquid chromatography tandem mass spectrometry (LC-MS/MS) technique for the analysis of trace levels of four tobaccospecific nitrosamines (TSNAs): nitrosoanabasine (NAB), nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and nitrosonornicotine (NNN). The technique can be applied for the analysis of TSNAs in USP grade nicotine. Nicotine used in e-liquids for the electronic smoking devices is typically obtained from tobacco plant materials (Nicotiana tabacum, Nicotiana rustica) and, although it is purified, it contains besides nicotine low levels of several contaminants such as minor alkaloids. It also contains traces of TSNAs. Analysis of TSNAs in USP grade nicotine is a challenging task since the analyzed samples contain about 10⁺⁷–10⁺⁸ times more nicotine than individual TSNAs. Because the analyzed solutions cannot be diluted too much in order to keep the TSNAs level above the limit of quantitation (LOQ), even for apparently good chromatographic separations, the peak tailing of nicotine may generate interferences. The new method of analysis uses a Luna Omega 1.6 μm particles chromatographic column for separation and detection on a LC-MS/MS instrument with scheduled multiple reaction monitoring (Scheduled MRM). The levels of TSNAs in nicotine of USP purity from four commercial sources varied between 3 to 8 ng/g NAB, 4 to 20 ng/g NAT, 30 to 50 ng/g NNK, and 0.5 to 2 ng/g for NNN. Besides the analysis of TSNAs in nicotine, the technique has been applied successfully in the analysis of TSNAs in e-liquids and in particulate phase generated by the electronic smoking devices.