Abstract
Two novel metabolites of the dipeptidyl peptidase inhibitor sitagliptin (MK-0431, (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)-butan-2-amine), were identified after purification from dog urine. The metabolites (referred to as M2 and M5) were characterized by hydrogen/deuterium exchange tandem mass spectrometry and NMR spectroscopy nuclear Overhauser effect experiments as the cis and trans stereoisomers formed by cyclization of the primary amino group with the alpha carbon of the piperazine ring, following oxidative desaturation.
Footnotes
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.106.013128.
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ABBREVIATIONS: MK-0431, (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2 -amine; HPLC, high-performance liquid chromatography; CID, collision-induced dissociation; NMR, nuclear magnetic resonance spectroscopy; NOE, nuclear Overhauser effect; DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide-1; H/D, hydrogen/deuterium; MS/MS, tandem mass spectrometry.
- Received September 27, 2006.
- Accepted December 15, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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