Long-retained metabolites of delta9- and delta8-tetrahydrocannabinols identified as novel fatty acid conjugates.

Long-retained metabolites of delta9-tetrahydrocannabinol (delta9-THC) and delta8-tetrahydrocannabinol (delta8-THC) previously detected in the liver, spleen, fat, and bone marrow of the rat after I.V. or I.P. injections of 14C-delta8-THC or 14C-delta9-THC, have been identified as fatty acid conjugates of 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC. Characterization of the metabolites was facilitated by their large-scale in vitro production from 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC with a rat-liver microsomal enzyme system. Conjugation of long-chain fatty acids to drugs or their hydroxylated metabolites may have considerable biological significance.