IDENTIFICATION AND MEASUREMENT OF 2 NEW METABOLITES OF NALTREXONE IN HUMAN URINE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 20  (3) , 413-433
Abstract
Two metabolites of naltrexone were identified in human and rat urine following drug administration. The metabolites, 2-hydroxy-3-0-methylnaltrexone and 2-hydroxy-3-0-methyl-6.beta.-naltrexol, were identified by comparison of their respective gas chromatographic retention times and methane chemical ionization spectral patterns with authentic standards. The standards were obtained by chemical synthesis from naltrexone. Urinary excretion of the 2 metabolites was measured by single ion recording of the pseudomolecular ions of the metabolites and an internal standard. Excretion data was collected from 5 human subjects over a 5-day period following a single dose of naltrexone. The metabolites, 2-hydroxy-3-0-methylnaltrexone and 2-hydroxy-3-0-methyl-6.beta.-naltrexol accounted for an average of 0.45 .+-. 0.08% and 4.6 .+-. 2.1% of the administered dose, respectively. An unusually long half-life of elimination of the latter metabolite (mean of 20.2 .+-. 1.8 h) was observed. Acid-hydrolysis of the samples failed to produce a significant increase of either metabolite indicating that the major portion of these metabolites is excreted in the free form. Naltrexone is a potent, orally effective narcotic antagonist.