Isolation and Characterization of Human Urinary Metabolites of Meclomen

Abstract

The principal metabolites of meclomen (sodium meclofenamate; sodium 2-[(2, 6-dichloro-3-methylphenyl)]aminobenzoate monohydrate) were isolated from human urine and characterized by gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy together with the Folin-Ciocalteu test. Oxidation occurred at the methyl group at C-3 and/or the aromatic ring in meclomen, yielding the methylol (M-1), dicarboxylic acid (M-2), phenols (M-3 and M-4), 3-hydroxymethylated phenol (M-7), 3-demethylated phenol (M-6) and phenolic dicarboxylic acid (M-8).Among these metabolites, M-1, M-2, M-3 and M-4 are common to fenamate antiinflammatory analgesics. A novel metabolite, M-6, is presumably produced from M-8 through M-7 or M-2 as an intermediate.