Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography–tandem mass spectrometry

A liquid chromatography–tandem mass spectrometric method was described to detect tobacco-specific nitrosamines (TSNAs) in replacement liquids of electronic cigarettes. Solid-phase extraction (SPE) and liquid–liquid extraction (LLE) were compared to each other to select the optimum clean-up method. Under the established condition, the limits of quantification of N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosoanabasine (NAB), and N′-nitrosoanatabine (NAT) were 0.06, 0.07, 0.06, and 0.04 μg/L respectively, by using 0.5 mL of replacement liquids, respectively, and the relative standard deviation was less than 10% at concentrations of 5.0 and 25.0 μg/L. The concentrations of TSNAs were measured in concentration ranges of 0.34–60.08 μg/L (64.8% detection frequency) for NNN, 0.22–9.84 μg/L (88.6% detection frequency) for NNK, 0.11–11.11 μg/L (54.3% detection frequency) for NNB, and 0.09–62.19 μg/L (75.2% detection frequency) for NAT in 105 replacement liquid brands from 11 electronic cigarette companies purchased in the Korean market.