ISOLATION OF TWO DIFFERENT GLUCURONIDE METABOLITES OF NALOXONE FROM THE URINE OF RABBIT AND CHICKEN

¹ Department of Pharmacology, Marquette School of Medicine, Milwaukee, Wisconsin

The rabbitt and the chicken were given large doses of naloxone hydrochloride and their urines were collected. After filtration, the urine samples were purified by absorbing the alkaloids on Amberlite XAD-2 resin columns and eluting them with methanol. A metabolite from rabbit urine was isolated after several steps involving removal and addition of different solvents, precipitation and filtration. Isolation of a metabolite from the chicken urine required additional steps including several extractions. The metabolite from the rabbit was naloxone-3-glucuronide and that from the chicken was N-allyl-14-hydroxy-7,8-dihydronormorphine-3-glucuronide. The base portion of both metabolites was liberated by acid hydrolysis and isolated. Infrared spectra of these bases, compared with those for the reference compounds, established their identification. These findings indicated that in the metabolite of the chicken, the 6-keto group of naloxone was reduced to an alcoholic group.