Identification of the in vivo liver metabolites of (--)-delta 7-tetrahydrocannabinol produced by the mouse.
The major in vivo metabolites of (--)-delta 7-tetrahydrocannabinol were extracted from the livers of mice after a single intraperitoneal dose and were examined by combined gas-liquid chromatography-mass spectrometry. Twenty-six metabolites were identified; most of these appeared to be produced via epoxidation of the double bond, although the epoxides themselves were not detected. Major metabolites involved hydroxylation of the double bond, to give the isomeric 1 alpha- and 1 beta, 7-dihydroxyhexahydrocannabinols. Of these, the 1 alpha, 7-isomer was the major product and appeared to be produced by hydrolysis of 1 alpha, 7-epoxyhexahydrocannabinol. It was further oxidized to 1 alpha-hydroxyhexahydrocannabinol-7-oic acid. Rearrangement of the epoxide to the 7-aldehyde and subsequent reduction to either the 7-alcohol or oxidation to the 7-acid was another major metabolic route. Derivatives of all these metabolites, hydroxylated in the 2"-, 3"- and 4"-positions of the sidechain were also identified. Allylic hydroxylation, predominantly at position 6, was also observed, but this was a relatively minor route. Reduction of the double bond yielded the isomeric axial and equatorial hexahydrocannabinols in low yield.
D000818:Animals; D013759:Dronabinol / Q000378:metabolism*; D004852:Epoxy Compounds / Q000302:isolation & purification; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D007536:Isomerism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice
D004852:Epoxy Compounds; D013759:Dronabinol