Revisiting the Metabolism of Ketoconazole Using Accurate Mass
2009
The microsomal metabolism of ketoconazole is revisited using accurate mass LC/MS n and deuterium labelling. Structures for sixteen metabolites are proposed from rat and human microsomal metabolism of commercial ketoconazole. Thirteen of the proposed structures are well determined and consistent with all data; five of the proposed structures are less certain. Ten of the metabolites are described for the first time. Reaction phenotyping shows that most of the metabo- lites arise from CYP3A4, the enzyme known to be well inhibited by ketoconazole.
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