title: General procedure for the isolation and identification of 6-alpha- and 6-beta-hydroxy metabolites of narcotic agonists and antagonists with a hydromorphone structure.
abstract: In order to aid in the elucidation of the metabolism of drugs containing the hydromorphone structure, a method is described for isolation from urine, separation and identification of the 6-alpha- and 6-beta-hydroxy metabolites. The samples were acid-hydrolyzed, extracted, and separated by thin-layer chromatography. The zone containing the hydroxy metabolites was removed and the compounds were re-extracted and analyzed by gas-liquid chromatography (GLC). Silylation of the extract was necessary in most cases for optimum GLC resolution of the alpha- and beta-hydroxy epimers. To demonstrate application of this method, the urine of guinea-pigs and rats which had received a single 40-mg dose of naloxone subcutaneously was analyzed. Analysis indicated a alpha/beta ratio of 0.41 for the guinea-pig. In contrast, the amount of 6-alpha-naloxol found in the urine of the rat was negligible in comparison with the 6-beta-hydroxy metabolite, indicating a species difference in the stereospecificity of the drug-metabolizing enzyme.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006900:Hydroxylation; D008722:Methods; D009019:Morphinans / Q000652:urine*; D009270:Naloxone / Q000652:urine; D009292:Narcotic Antagonists / Q000652:urine*; D051381:Rats; D013237:Stereoisomerism
chemical_list: D009019:Morphinans; D009292:Narcotic Antagonists; D009270:Naloxone