Disposition of Cannabichromene, Cannabidiol, and Δ9-Tetrahydrocannabinol and its Metabolites in Mouse Brain following Marijuana Inhalation Determined by High-Performance Liquid Chromatography-Tandem Mass Spectrometry

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for the analysis of marijuana cannabinoids in mouse brain tissue using an Applied Biosystems 3200 Q trap with a turbo V source for TurbolonSpray attached to a Shimadzu SCL HPLC system. The method included cannabichromene (CBC), cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), 11-hydroxytetrahydrocannabinol (11-OH-THC), and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). These compounds were isolated by liquid-liquid extraction using cold acetonitrile. The following transition ions were monitored by multiple reaction monitoring (MRM): m/z 315>193, 315>259 for THC/CBD/CBC; m/z 331>193, 331>105 for 11-OH-THC; m/z 345>299, 345>193 for THC-COOH; m/z 318>196 for THC-d3; m/z 334>196 for 11-OH-THC-d3, and m/z 348>302 for THC-COOH-d3. Linearity for THC, 1-OH-THC, and THC-COOH was 1–200 ng/g; for CBC and CBD, it was 0.5–20 ng/g. Within-run and between-run precisions for all the analytes yielded coefficients of variation of < 20%. Four C57BL6 mice were sacrificed 20 min after nose-only exposure to the smoke of 200 mg of marijuana containing 0.44 mg CBC, 0.93 mg CBD, and 8.81 mg THC. The mean brain concentrations were 3.9 ± 1.5 ng/g CBC, 21 ± 3.9 ng/g CBD, 364 ± 74 ng/g THC, and 28 ± 5.9 ng/g 11-OH-THC. THC-COOH was not detected. The relative mean brain cannabinoid concentrations correlated to the amounts of the cannabinoids in the inhaled marijuana.