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.
Zhang
Donglu
D
Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research & Development, Princeton, NJ 08543, USA.
Cheng
Peter T
PT
Zhang
Haiying
H
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D005243:Feces / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010080:Oxazoles / Q000493:pharmacokinetics*; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists
D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D005998:Glycine; C500085:muraglitazar