Stability of cannabidiol, ∆9-tetrahydrocannabinol, and cannabinol under stress conditions

The aim of this work was to validate a high-performance liquid chromatography (HPLC) method for determination of the stability of cannabidiol, ∆9-tetrahydrocannabinol, and cannabinol. Furthermore, degradation kinetics were also investigated. Five stress conditions—acid degradation, alkaline degradation, oxidation, thermal degradation, and photodegradation—were evaluated. The results showed that the HPLC method had a linear response (R2 ≥ 0.9999) in the test range of 1–200 µg/mL. The method was specific, precise, and accurate. The limits of both detection and quantitation are also reported. According to the stress test, the three cannabinoids (cannabidiol, ∆9-tetrahydrocannabinol, cannabinol) were stable during exposure to a range of thermal conditions for 24 h. They were unstable when being subjected to acid conditions; cannabidiol under alkaline conditions was extremely unstable. Degradation kinetic analysis demonstrated that the compounds remained at a level of approximately 8% after 5 h, and approached a first-order reaction (R2 = 0.9930) with a rate constant of − 0.5057 h− 1. In summary, the obtained data can be used as a guide for the formulation development of cannabis products in order to maintain their active compounds as well as their activities.