Tentative identification of phase I metabolites of HU-210, a classical synthetic cannabinoid, by LC-MSMS.
(6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzocchromen-1-ol (HU-210) is a synthetic cannabinoid, with a classical cannabinoid structure similar to Δ(9)-tetrahydrocannabinol (Δ(9)-THC). In this study, the in vitro metabolism of HU-210 was investigated in human liver microsomes to characterize associated phase I metabolites. HU-210 was incubated with human liver microsomes, and the reaction mixture was analyzed using LC-MSMS. HU-210 was metabolized in human liver microsomes, yielding about 24 metabolites. These metabolites were structurally characterized on the basis of accurate mass analyses and MSMS fragmentation patterns. The major metabolic route for HU-210 was oxygenation. Metabolites M1-M7 were identified as mono-oxygenated metabolites M8-M15, mono-hydroxylated metabolites M16-M20, di-oxygenated metabolites and M21-M24, di-hydroxylated metabolites. These results provide evidence for in vivo HU-210 metabolism, and they may be applied to the analysis of HU-210 and its relevant metabolites in biological samples.