In vitro metabolism of cannabigerol in several mammalian species.
Microsomal incubations were prepared from the livers of male mice, rats, cats, guinea-pigs, hamsters and gerbils and both male and female rabbits and were incubated with cannabigerol (CBG), a constituent of marihuana. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined as trimethylsilyl (TMS) and (2H9)TMS derivatives by gas chromatography/mass spectrometry. Structural elucidation was aided by hydrogenation of the metabolites to tetrahydro derivatives. Similar metabolites were produced by each of the species but the ratios of the individual compounds differed considerably. Twelve metabolites were identified. The major metabolites were monohydroxy compounds with the hydroxyl group at C-8', C-9', C-4' or at one of any position of the pentyl chain. Reduction of the delta-6' double bond was prominent in the cat to give 8'-hydroxy-6',7'-dihydro-CBG. The other major metabolic route was epoxidation of this double bond and hydrolysis to give 6',7'-dihydroxy-6',7'-dihydro-CBG. Although epoxidation of the other double bond was detected, the resulting metabolite was present in low concentration and hydrolysis was not observed. The mass spectral fragmentation of CBG and its metabolites was dominated by formation of the tropylium ion by cleavage of the C-1'--C-2' bond and by ions formed by cleavage of the C-3'--C-4' and C-4'--C-5' bonds. In addition, compounds containing hydroxylation at C-1"--C-4" (pentyl chain) gave rise to the same abundant diagnostic ions that have been observed for corresponding metabolites of other cannabinoids.
Harvey
D J
DJ
University Department of Pharmacology, Oxford, UK.
Brown
N K
NK
D000818:Animals; D002186:Cannabinoids / Q000032:analysis / Q000378:metabolism*; D002384:Catalysis; D002849:Chromatography, Gas; D006224:Cricetinae; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005849:Gerbillinae; D006168:Guinea Pigs; D006865:Hydrogenation; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014297:Trimethylsilyl Compounds
D002186:Cannabinoids; D014297:Trimethylsilyl Compounds; C037036:cannabigerol