In vitro metabolism of cannabidiol in the rabbit: identification of seventeen new metabolites including thirteen dihydroxylated in the isopropenyl chain.
The metabolism of cannabidiol (CBD) was studied in liver microsomes from the female New Zealand white rabbit. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined as trimethylsilyl (TMS), methyl ester/TMS and (2H9)TMS derivatives by gas chromatography/mass spectrometry. Thirty-nine metabolites, mainly mono-, di- and tri-hydroxy compounds, were identified; 17 of these have not been reported before. New metabolites included 8,9-dihydroxy-8,9-dihydro-CBD (two isomers) and seven monohydroxy derivatives of each of these two compounds. The mass spectra of the TMS derivatives of metabolites not hydroxylated in the isopropenyl group were generally dominated by the ion produced by retro-Diels-Alder cleavage of the terpene ring. Other structurally informative ions included the tropylium ion and fragments diagnostic of hydroxylation at C-1", C-2", C-3", C-4" and C-7. The spectra of the TMS derivatives of metabolites hydroxylated in the isopropenyl group were generally dominated by the ion at m/z 143. This involved loss of CH2OTMS and a retro-Diels-Alder fragmentation analogous to that seen in the other metabolites, but with charge retention by the other (smaller) fragment. Other, related fragment ions also characterized these metabolites.
Harvey
D J
DJ
University Department of Pharmacology, Oxford, UK.
Brown
N K
NK
D000818:Animals; D001711:Biotransformation; D002185:Cannabidiol / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D002849:Chromatography, Gas; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D011817:Rabbits; D014297:Trimethylsilyl Compounds / Q000032:analysis
D014297:Trimethylsilyl Compounds; D002185:Cannabidiol