Analytical Studies on Mepirizole and Its Metabolites. II. Identification of the Human Urinary Metabolites of Mepirizole with Stable Isotope Labeling

Abstract

The metabolism of mepirizole (I) in human urine was studied by labeling the drug with a stable isotope, deuterium. An equimolar mixture of the deuterium labeled mepirizole (II) and its protium counterpart (I) was administered orally to a man. The metabolites were extracted from the pooled urine with CH₂Cl₂, treated with diazomethane and applied to GC-MS. The ion clusters in the mass spectra were used for detection of the urinary metabolites of I in man. By this technique, three metabolites, 1-(4-methoxy-6-methyl-2-pyrimidinyl)-5-methoxy-3-hydroxymethylpyrazole (III), 1-(4-methoxy-6-methyl-2-pyrimidinyl)-5-methoxypyrazole-3-carboxylic acid (IV) and 1-(4-methoxy-6-carboxy-2-pyrimidinyl)-5-methoxy-3-methylpyrazole (V) were identified in human urine.