PT  - JOURNAL ARTICLE
AU  - D J Harvey
TI  - Oxidative cleavage of the pentyl side-chain of cannabinoids. Identification of new biotransformation pathways in the metabolism of 4&#039;-hydroxy-delta-9-tetrahydrocannabinol in the mouse.
DP  - 1990 May 01
TA  - Drug Metabolism and Disposition
PG  - 350--355
VI  - 18
IP  - 3
4099  - http://dmd.aspetjournals.org/content/18/3/350.short
4100  - http://dmd.aspetjournals.org/content/18/3/350.full
SO  - Drug Metab Dispos1990 May 01; 18
AB  - During an investigation of the mechanisms leading to the formation of metabolites of cannabinoids in which the pentyl side chain is reduced to 2, 3 or 4 carbon atoms, the further metabolism of 4&#039;-hydroxy-delta 9-tetrahydrocannabinol was investigated in vivo in mice. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS. Ten metabolites were identified and a further two had tentative structural assignments made. The major metabolic route, in common with that seen with most cannabinoids, was hydroxylation at the allylic 11-position, followed by oxidation to a carboxylic acid. Additional hydroxylation occurred at C-8. Abundant metabolites were also formed by oxidative cleavage of the pentyl side chain. The major metabolites of this type had lost the terminal two carbon atoms to give compounds containing a carboxyethyl side chain. This is the major product normally produced by beta-oxidation of the acid formed from 5&#039;-hydroxy-delta 9-tetrahydrocannabinol. Trace concentrations of two other acids that appeared to have a carboxypropyl side chain were also found. The results show that, in addition to beta-oxidation, initiated by hydroxylation at the 5&#039;-carbon atom (omega-hydroxylation), at least one other oxidative route, initiated by omega-1-hydroxylation, is involved in the production of metabolites with two carbon atoms missing from the pentyl side chain. This pathway does not seem to have been characterized as a biotransformation mechanism in drug metabolism and a possible mechanism is suggested.