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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-α- and 6-β-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 α-and β-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 α/β ratio of 0.41 for the guinea-pig. In contrast, the amount of 6-α-naloxol found in the urine of the rat was negligible in comparison with the 6-β-hydroxy metabolite, indicating a species difference in the stereospecificity of the drug-metabolizing enzyme.
Published Version
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