Glycidol, a thermal degradant of glycerol, is a proposed addition to the established U.S. Food and Drug Administration (FDA) Harmful or Potentially Harmful Constituents (HPHC) and is also listed for consideration within the FDA Guidance for Premarket Tobacco Product Application for Electronic Nicotine Delivery Systems (ENDS). Due to its chemical instability, Glycidol is a challenging compound to analyze and, at present, no standardized method exists for the determination of this compound.

The objective of this work was to develop and validate a stable, sensitive, and selective method for the determination of glycidol in e-liquid and aerosol samples utilizing a derivatization methodology via gas chromatography-mass spectrometry (GC-MS). This new method involves an aliquot of e-liquid and/or collection of trapped aerosol onto a Cambridge Filter Pad (CFP) followed by extraction using acetone spiked with deuterated glycidol as an internal standard. The extraction solution is then transferred to a vial containing p-Toluenesulfonyl chloride and concentrated Hydrogen Bromide (HBR) to form the Bromo-p-toluenesulfonate derivative followed analysis via GC-MS.

The calibration range was from 10 ng/mL to 800 ng/mL, with a quantification (LOQ) equivalent to 180 ng/g for e-liquids and 250 ng/collection for aerosols. All requirements for method validation were met including specificity, accuracy, precision, repeatability, robustness, and stability. An assessment of whole pod glycidol measurements were conducted on nine commercially available disposable ENDS products using the ISO 20768 standard puffing regime. Results of these samples ranged from 1.64 to 329 ng/puff. In conclusion, this method is deemed fit for purpose to accurately determine trace amounts of glycidol in both e-liquids and aerosol samples.