Application of PTR‑ToF‑MS for detecting and tracking e‑liquid aroma compounds in exhaled breath

Real-time characterization of e-cigarettes chemical constituents' persistence in the respiratory tract is essential for exposure assessment and health risk evaluation, but has not been previously demonstrated. In this study, proton transfer reaction - time‑of‑flight - mass spectrometry (PTR‑ToF‑MS) is integrated with multivariate statistical analysis to select volatile and semi‑volatile organic compounds from commercially available e‑liquid products and to track their washout kinetics. Participants (N = 10) inhaled single puffs from an e-cigarette loaded with unflavoured e-liquid base, or cinnamon, or peppermint/menthol flavour. Exhaled breath samples were collected before and after e-cigarette puff and subsequently analyzed with PTR-ToF-MS. Multivariate analysis identified compounds significantly elevated post-vaping (VIP>1, p<0.05), including flavour components and potential thermal degradation products. Real-time washout monitoring (N = 3) revealed that e-liquid-related VOCs can be retained for up to 32 minutes post-vaping, though substantial inter-individual variability was observed. These findings demonstrate the potential of PTR-ToF-MS as a non-invasive tool for real-time breath analysis of e-cigarette exposure, providing insight into the short-term kinetics and retention of e-cigarette constituents. This approach is well-suited for application in larger cohort studies aimed at exposure assessment and toxicokinetic evaluation.