Human metabolism of tolfenamic acid. II. Structure of metabolites and C-13 NMR assignments of fenamates

Metabolites of tolfenamic acid appearing in human urine have been isolated and their structures determined by C-13 nuclear magnetic resonance and gas chromatography-mass spectrometry. Comparative studies on tolfenamic, mefenamic, and flufenamic acids in conjunction with the metabolites have permitted complete C-13 NMR assignments for this series of compounds. Five metabolites identified included three that were monohydroxylated, one that was both methoxylated and hydroxylated, and another in which the methyl group was oxidized to a carboxyl group. The information presented on the fenamate standards and the metabolites represents an excellent basis for structural elucidation of other fenamates and their metabolites.