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Metabolite Profiling Using Human Hepatocyte Co-cultures and UHPLC-QTOF-MS with Data Independent MS/MS

The identification of human derived metabolites is an imperative step in drug discovery and development process. Typical studies are conducted in human in vitro systems and metabolites are identified utilizing HPLC-MS/MS. Human hepatocyte co-culture is a new in vitro system, which is comprised of a mixture of hepatocytes and fibroblast cells, capable of remaining viable and highly functional for up to 4 weeks. In this presentation, the application of high resolution mass spectrometry (HRMS), ultrahigh-pressure liquid chromatography (UHPLC), full scan acquisition, and Sequential Window acquisition of All THeoretical fragment ion spectra (SWATH™) was used to profile and characterize metabolites of diclofenac, linezolid, and ziprasidone following incubations in human hepatocyte co-cultures.

 

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