Analysis of vaporized caffeine in smoke from e-cigarettes using liquid chromatography-tandem mass spectrometry and clarification of minor components.

PURPOSE: Electronic cigarettes (e-cigarettes) are used widely, and e-cigarettes containing caffeine (Caf) have recently become commercially available. However, no risk evaluation of these Caf-containing products has been performed to date. Such an evaluation requires a sensitive analytical method for quantifying Caf in smoke from e-cigarettes. The aim of this study was to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying vaporized Caf from commercially available e-cigarettes, and to determine minor components related to Caf in cigarette smoke extract (CSE). METHODS: A sampling system for Caf using a suction pump was designed and sampling conditions were optimized. RESULTS: The optimized LC-MS/MS conditions allowed the sensitive determination of Caf in smoke with a limit of detection of 0.03 ng/mL at a signal-to-noise ratio of 3. The method was applied to CSEs from five e-cigarette products and the concentration of Caf ranged from 0.894 ± 0.090 to 3.32 ± 0.14 µg/mL smoke (n = 3). Additionally, minor components related to Caf, such as theobromine, theophylline, and paraxanthine, were detected in CSE and in e-liquid at very low concentrations, indicating that they were impurities in e-liquid and vaporized along with Caf. CONCLUSION: This is the first report to determine the concentration of vaporized Caf using an LC-MS/MS method and to clarify several minor components in smoke from e-cigarettes.