ISSN: 2157-7609
+44-77-2385-9429
Catherine Henderson
United Kingdom
Research Article
Identification of Novel Metabolic Pathways of Sitagliptin (STG) by LC/MS and LC/MS2 after Incubations with Rat Hepatocytes
Author(s): Osama IG Khreit, Helen M Grant, Catherine Henderson, David G Watson and Oliver B Sutcliffec
Osama IG Khreit, Helen M Grant, Catherine Henderson, David G Watson and Oliver B Sutcliffec
Sitagliptin (STG), a drug for treating Type Ii Diabetes Mellitus (T2DM), has been associated with severe joint pain in some patients. In this paper the metabolic profile of the drug has been investigated in order to determine metabolism and formation of reactive compounds which may contribute to this adverse effect. Metabolism of STG was investigated in vitro by incubation with freshly isolated Sprague-Dawley rat hepatocytes, to characterize Phase I and II metabolites, and the reaction mixture analysed on a zwitter ionic hydrophilic interaction (ZIC®-HILIC) column using LC-MS and LC-MS2 utilising electrospray ionization (ESI) in the positive ion mode.
STG was metabolised to yield eleven metabolites, but in total only 3.1% of the parent drug was metabolised over 2 hrs incubation. These metabolites were structurally characterized on the basis of accurate mass analyses and .. View More»
DOI:
10.4172/2157-7609.1000220