Effect of O-acetylation on ketene and carbonyl yields from conventional and emerging cannabinoids

Abstract

The pulmonary toxicant, ketene, has been observed from electronic (e-) cigarette vaping and dabbing (flash vaporisation) of acetylated compounds such as Vitamin E Acetate (VEA) and the O-acetates of select few cannabinoids. Yet for the majority of commercially-available cannabinoids with structural similarities to VEA, toxicant yields from vaping have not been quantified. Methodology optimisation for ketene trapping and quantification and characterisation of the co-production of other potentially harmful products have not been reported. In this work, an optimised impinger collection method was used to quantify the yield of ketene and carbonyl products from several conventional and emerging cannabinoid distillates using a commercially available cannabis e-cigarette. Ketene and carbonyls were analysed after chemical derivitisation by high performance liquid chromatography high-resolution mass spectrometry (HPLC-HRMS) and cannabinoids were analysed using gas chromatography mass spectrometry (GC-MS). The cannabinoids under study are: delta-8 tetrahydrocannbinol O-acetate (Δ8-THCO), delta-9 tetrahydrocannbinol O-acetate (Δ9-THCO), cannabidiol di-O-acetate (CBD-di-O), cannabigerol di-O-acetate (CBG-di-O), 9(R)-hexahydrocannabinol O-acetate (HHCO) and their paired non-acetylated analogues (Δ8-THC, Δ9-THC, CBD, CBG, and HHC). The acetyl group decomposed into ketene during vaping with nearly quantitative efficiency (> 99%). No ketene was observed in the unvaped distillates or during vaping of the the non-acetylated cannabinoids. The highest summed production of ketene and carbonyl was observed from CBD-di-O which was attributed to the presence of two O-acetate groups on the phenyl moeity and the reactive exo-cyclic double bond of the terpene side chain. Higher airflow through the device due to opening the vent reduced ketene yields but increased carbonyl yields, showcasing that temperature and oxygen influence the distribution of these toxicants. Cannabis vape users can oscillate between open and closed air vents, which modify their toxicant exposure. Overall, ketene and carbonyl production yields from o-acetylated cannabinoids ranged between 1-4 % and 0.1-1.5 %, respectively, by cannabinoid mass. The carbonyl production yields for non-acetylated cannabinoids ranged between 0.1 – 7 % by cannabinoid mass. These optimised measurements show that vape users can be exposed to yields of toxicants that far exceed safety limits for pulmonary effects, and therefore, further stringent product regulation is required to avoid health implications from vaping.