Rapid LC–QTOF–MS screening method for semi-synthetic cannabinoids in whole blood

Semi-synthetic cannabinoids are a class of new psychoactive substances (NPSs) with structural similarities to the main psychoactive phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) found in Cannabis sativa L. The first semi-synthetic cannabinoids, which were used as legal substitutes for marijuana were Δ8-tetrahydrocannabinol (Δ8-THC) and hexahydrocannabinol (HHC). Δ8-THC emerged around 2019 on the recreational drug market in the United States after it became legal due to an ambiguity in the Agricultural Improvement Act 2018 (Farm Bill 2018). It was never legal outside the United States as the isomers of THC are regulated in the United Single Convention on Narcotic Drugs from 1971. HHC, a hydrogenated derivative of THC, followed as a legal substitute on the European recreational drug market. Many countries already placed HHC in their narcotic substance law, which lead to the emergence of other structurally related derivatives of THC. An existing rapid screening method for the qualitative analysis of various new psychoactive substances was expanded for semi-synthetic cannabinoids in whole blood using a LC-QTOF-MS system. This method was validated for 24 different phytocannabinoids and semi-synthetic cannabinoids in blood. Recovery rates of the analytes from a liquid-liquid-extraction ranged from 87-118%, matrix effects ranged from 24-93%, and limits of detection (LOD) ranged from 0.8-16 ng/mL.