Peroxisome proliferator-activated receptor-δ (PPARδ) agonists are the drug candidates with potential performance-enhancing properties, and therefore their illegitimate use in sports should be controlled. To simulate the metabolism of PPARδ agonist GW0742, in vitro reactions were performed which demonstrated that the main metabolic pathway is oxidation of the acyclic divalent sulfur to give the respective sulfoxide and sulfone. After being characterized by liquid chromatography-mass spectrometry (LC-MS), these metabolites were evaluated in urine samples collected after a controlled excretion study. For comparative purposes, GW1516 excretion study was also performed. It has been shown that GW1516 and GW0742 are best monitored as the sulfone metabolites which are detectable in urine using LC-MS/MS based procedure up to 40 and 20 days after a single oral dose of 15 mg each, respectively. The unmetabolized compounds are measurable only for a short period of time and at low ng/ml level. The sulfoxide-to-sulfone ratio for both GW1516 and GW0742 changed irregularly in the range of 1:3 to 1:15 depending on time elapsed after administration with a tendency of increasing the ratio with time. The other important finding was that the abundance of GW0742 and its metabolites in urine is about ten times lower than in case of GW1516.
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