DMPK

In vitro Species Comparison using Long-term Hepatocyte Co-Culture Models and Highly Sensitive UHPLC-Q-TOF-MS with SWATH Analysis - April, 2014

One of the main goals of in vitro species comparison studies is to assess whether there is adequate coverage from the preclinical species to humans with respect to disproportional and/or unique human metabolites. Traditionally, this is performed with liver microsomes or hepatocytes; however, these short-term in vitro systems do not usually provide multi-generation metabolites. In this poster abstract, we present the incubation of selected compounds (linezolid, ziprasidone, and diclofenac) that have diverse chemical structures that are subjected to a wide range of biotransformation pathways with hepatocyte co-culture models over an extended time period, and mined the metabolite data with UHPLC-Q-TOF-MS and Sequential Windowed Acquisition of Theoretical Fragments (SWATH) analysis to compare the in vitrometabolite profiles to those found in humans in vivo.

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