Characterization of the metabolites of GW1929 in rat by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Rationale: GW1929 is a potent PPAR-γ activator. To fully understand its mechanism of action, it is necessary to study the in vitro and in vivo metabolism.

Methods: For in vitro metabolism, GW1929 was incubated with rat hepatocytes at 37°C for 2 h. For in vivo metabolism, rats were orally administered with GW1929 at a single dose of 10 mg/kg and plasma, urinary and fecal samples were collected at defined time points. All the samples were analyzed by the developed ultra-high-performance liquid chromatography combined with tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and product ions.

Results: A total of 17 metabolites, including seven glucuronide conjugates, were detected and structurally identified. M4 (hydroxylation), M13 (demethylation) and M14 (hydroxylation) were the most abundant metabolites. The metabolic pathways of GW1929 referred to hydroxylation, demethylation, deamination and glucuronidation.

Conclusions: The present study provided new information on the in vitro and in vivo metabolic profiles of GW1929 which will be helpful for a better understanding of the mechanism of the elimination of GW1929.