Abstract
Two potential anti-asthmatic α-methylacetohydroxamic acids, compound I and compound II were metabolised to two major products (metabolite 1 and metabolite 2) after oral dosing to rabbits. Metabolite 1, extracted under acid conditions from the plasma and urine of dosed animals, was identified as a glucuronide by incubation with β-glucuronidase and subsequent high-performance liquid chromatographic—mass spectrometric (HPLC—MS) analysis of the aglycone. HPLC—MS analysis of metabolite 2 suggested that it was the acetamide, however, unequivocal identification was obtained by further analysis using gas chromatography—mass spectrometry (GC—MS) of its trimethylsilyl derivative and by comparison with the mass spectra of the authentic acetamides. This study shows the advantages of combining HPLC—MS with other techniques such as GC—MS for the identification of metabolites.
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