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

Drug Metab Lett. 2007 Dec;1(4):287-92. doi: 10.2174/187231207783221466.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods*
  • Feces / chemistry
  • Glycine / analogs & derivatives*
  • Glycine / pharmacokinetics
  • Humans
  • Mass Spectrometry / methods*
  • Oxazoles / pharmacokinetics*
  • PPAR alpha / agonists
  • PPAR gamma / agonists

Substances

  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Glycine
  • muraglitazar