Mass Defect Filtering on High Resolution LC/MS Data as a Methodology for Detecting Metabolites with Unpredictable Structures: Identification of Oxazole-Ring Opened Metabolites of Muraglitazar

This study describes the application of the mass defect filter method for the detection of two unpredicted oxazole-ring opened metabolites of muraglitazar in the feces of humans following oral administration. Unlike other muraglitazar metabolites, these metabolites formed little to no protonated ions, and the NH(4)(+) or Na(+) adduct ions that were formed were weak and not discernible from fecal interferences even after background subtraction. With mass defect filtering on high resolution LC/MS data, the resulting total ion chromatogram and the simplified mass spectra allowed for the identification and characterization of these metabolite ions, and their structures were confirmed by synthesis.