HPLC Analyses of CBD Oral Formulation Content Recovery Under Simulated Biological Conditions

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid derived from Cannabis sativa that has gained widespread popularity for both medical and recreational uses. CBD in the form of an oral solution is approved by the Food and Drug Administration (FDA) as Epidiolex for the treatment of certain seizure conditions, but CBD is also sold in numerous hemp-derived non-pharmaceutical products that are not approved by the FDA. Following the legalization of CBD products containing less than 0.3% tetrahydrocannabinol (THC), the market has expanded rapidly, leading to the incorporation of CBD into oils, capsules, topical formulations, foods, beverages, and vaping products. However, unlike conventional FDA-approved pharmaceuticals, many over-the-counter CBD products are manufactured without standardized quality control measures, potentially resulting in variability in cannabinoid content and subsequently CBD bioavailability and biological effects. Here, we use in-house reversed-phase high-performance liquid chromatography (HPLC) for accurate and reproducible comparison of CBD recovery under organic-solvent extraction and simulated biological fluid from commercially available non-pharmaceutical CBD products. All five tested hemp products yielded CBD contents that fell within the expected range of the labeled amount when extracted using a methanol and isopropanol mixture. However, there was a wide range of variability in CBD recovery when the same products were extracted under identical conditions using simulated gastric, intestinal, or sublingual fluids. This study provides further evidence that standardized manufacturing practices to govern the processing and development of hemp-derived CBD products need to be developed to ensure adequate release of CBD into biological fluids, thereby increasing the potential for high CBD bioavailability and accurate dosing.