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.
Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research & Development, Princeton, NJ 08543, USA.
Donglu
D
Zhang
Peter T
PT
Cheng
Haiying
H
Zhang
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