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In vivo metabolism of the ethyl homologues of delta‐8‐tetrahydrocannabinol and delta‐9‐tetrahydrocannabinol in the mouse
Author(s) -
Brown N. K.,
Harvey D. J.
Publication year - 1991
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200200514
Subject(s) - metabolite , ethyl acetate , chemistry , metabolism , sephadex , chromatography , delta , biochemistry , enzyme , engineering , aerospace engineering
Abstract Ethyl‐delta‐8‐tetrahydrocannabinol (ethyl‐delta‐8‐THC) and ethyl‐delta‐9‐THC were synthesized by condensation of 5‐ethyl‐1,3‐dihydroxybenzene and 1S‐ cis ‐verbenol. The two cannabinoids were administered to male Charles River CD‐1 mice and hepatic metabolites were extracted with ethyl acetate and isolated by chromatography on Sephadex LH‐20. Metabolite identification was by gas chromatography/mass spectrometry as trimethylsilyl (TMS), ( 2 H 9 )TMS, methyl ester/TMS and dihydro/TMS derivatives. Metabolites from ethyl‐delta‐8‐THC, of which six were identified, were similar with respect to the positions substituted on the terpene ring to those produced by higher homologues; the major metabolite, accounting for about 95% of the metabolic fraction, was ethyl‐delta‐8‐THC‐11‐oic acid. Side‐chain hydroxy metabolites were not detected. Metabolism of ethyl‐delta‐9‐THC was also similar to that of the higher homologues with the exception that less metabolism occurred at C‐8 and a higher percentage of the total metabolic fraction was accounted for by the 11‐oic acid metabolite. Five metabolites were identified; minor metabolites were mainly dihydroxylated compounds and hydroxylated derivatives of ethyl‐delta‐9‐THC‐11‐oic acid. A dihydro‐metabolite, the C‐9‐axial‐COOH isomer of ethyl‐hexahydrocannabinol‐11‐oic acid, was produced by both compounds and a trace of ethyl‐CBN‐11‐oic acid was produced by ethyl‐delta‐9‐THC.