Mechanism of hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol to 11-oxo-delta 8-tetrahydrocannabinol. Evidence for hydration of the aldehyde formed.
Hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC) to 11-oxo-delta 8-THC was investigated. Hepatic microsomes from mice, rats, guinea pigs and rabbits catalyzed the oxidation of 11-OH-delta 8-THC to 11-oxo-delta 8-THC together with the formation of dihydroxy-delta 8-THCs oxidized at the 7-position or at the pentyl side chain of 11-OH-delta 8-THC. 11-Oxo-delta 8-THC formed under oxygen-18 gas was analyzed by gas chromatography-mass spectrometry (GC-MS) indicating that molecular oxygen was not significantly incorporated into the aldehyde formed. 11-Oxo-delta 8-THC formed from 11-18OH-delta 8-THC (18O/16O = 0.81 - 1.05) was also found to lose oxygen-18 from the molecule. These results suggest that 11-oxo-delta 8-THC is hydrated in the incubation mixture and the aldehyde oxygen is exchangeable with the oxygen atom of water. When 11-oxo-delta 8-THC was incubated with hepatic microsomes and phosphate buffer containing H2 18O (44 atom%), GC-MS analysis indicated the incorporation of oxygen-18 into the aldehyde recovered from the incubation mixture. The results suggest that the hepatic microsomes may facilitate the hydration of 11-oxo-delta 8-THC and exchange an oxygen atom of the aldehyde group with that of water in the incubation mixture.
Watanabe
K
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Matsunaga
T
T
Narimatsu
S
S
Yamamoto
I
I
Yoshimura
H
H
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C020443:11-oxo-delta(8)-tetrahydrocannabinol; D013759:Dronabinol