Characterizing the degradation of cannabidiol in an e-liquid formulation

The reported characteristics of cannabidiol (CBD) have encouraged significant growth in commercial CBD products. There is limited information on the stability of CBD and some researchers have noted significant reductions of CBD in products. In this study, the chemical profiles of plant-based and chemically synthesized CBD in a prototype e-liquid formulation were assessed during 4 weeks of storage under varying conditions. Samples were analysed on days 1, 8, 15, 22, and 29 by untargeted analysis using ultra-high performance liquid chromatography-trapped ion mobility-time-of-flight mass spectrometry (UHPLC-TIMS-TOF-MS). On day 1, analysis of plant-based and synthetic CBD formulations showed small differences in their composition, with plant-based CBD e-liquid containing trace levels of a higher number of phytocannabinoid-related impurities. Storage for 4 weeks under stress (40 °C, 75% relative humidity, dark) and ambient (25 °C, 60% relative humidity, daylight) conditions led to increases in the number and abundance of cannabinoid-related degradation products, including cannabielsoin (CBE) and CBD-hydroxyquinone (HU-331), which are products of the oxidation of CBD, and other unidentified cannabinoid-related compounds. The unidentified cannabinoid-related compounds were probed by accurate mass measurement and MS² fragmentation but could not be matched using a mass spectral library derived from 39 commercially available cannabinoid reference standards. Based on elemental composition and MS² fragmentation patterns, the unidentified cannabinoid-related compounds were classified as hydroxy-CBE, hydroxy-CBD, and dihydroxy-CBD. The analysis of e-liquid formulations protected from light and stored at 4 °C for 4 weeks indicated only very small increases in CBD oxidation products. The results indicate that CBD degrades in e-liquid solution at ambient temperature in dark and light to form potentially undesirable products, including cannabielsoin and cannabidiol hydroxyquinone.