Identification of isopropylantipyrine metabolites in rat and man by using stable isotope tracer techniques.

Abstract

The metabolites of isopropylantipyrine (IPA) were identified in urine of rats by gas chromatography-mass spectrometry (GC-MS) combined with stable isotope tracer techniques. After the oral administration of an equimolar mixture of IPA and IPA-1-C6D5, the urinary metabolites were extracted with chloroform before or after hydrolysis with β-glucuronidase. The extracts were subjected to GC-MS after trimethylsilylation. Characteristic doublet peaks in the mass spectra indicated the presence of 13 metabolites in the urine. The metabolized positions were determined on the basis of the retained numbers of deuterium atoms after the administration of various deuterated IPAs, i.e., IPA-2-CD3, IPA-3-CD3 and IPA-4-CH (CD3)2. The identified metabolites were oxidation products of the phenyl, 2-methyl, 3-methyl and isopropyl groups and of the C-4 position of the pyrazolone ring. In humanurine, one major metabolite, hydroxyphenyl-IPA, and four minor metabolites were detected after administration of IPA.