The power of using a stable isotope analog of propylene glycol (¹³C₃-PG) in eCigarettes was demonstrated during the TSRC last year. From a clinical study we monitored the pharmacokinetics of propylene glycol (PG), ¹³C₃-PG and nicotine in both vapers and non-vapers. The data demonstrated that the second-hand exposure of non-vapers to ¹³C₃-PG was 1/5000 that of the vapers. We selected ¹³C₃-PG instead of deuterated PG as our stable isotope analog because ¹³C₃-PG might afford us the opportunity to monitor metabolites, degradants, or toxicants, such as ¹³C₂-acetaldehyde and ¹³C₁-formaldehyde in biofluids. In a letter to the New England Journal of Medicine entitled “Hidden Formaldehyde in e-Cigarette Aerosols”, the authors reported the detection of formaldehyde hemiacetal in the aerosolized liquid from eCigarettes under high voltage conditions. Detection of compounds related to known toxicants in eCigarette vapor increases the importance of measuring toxicants from ¹³C₃-PG in biofluids to determine exposure levels under typically pleasurable vaping conditions. The measurement of acetaldehyde and formaldehyde in biofluids presents many bioanalytical challenges. First, their small atomic mass and highly polar nature make them very susceptible to interference and matrix effects using traditional LC-MS/MS. Second, aldehydes are chemically reactive with nucleophilic groups such as amines. And third, there are 19 aldehyde dehydrogenase (ALDH) isoforms in humans. While most ALDH isoforms are intracellular, some ALDH activity may be present in plasma which would adversely affect acetaldehyde and formaldehyde stability. Consequently, we chose to determine the exposure level of ¹³C₂-acetaldehyde and ¹³C₁-formaldehyde in plasma using their glutathione conjugates.