Metabolic Stability Assay Using Human Hepatocyte Co-cultures and Integrated Qualitative/Quantitative High Resolution Mass Spectrometry - April, 2014

Traditional metabolic stability methodology using suspended hepatocyte for drug candidates screening are limiting in their ability to accurately predict clinical outcomes. Hepatocyte co-culture platform is a bioengineered, in vitro system with a defined cyto-architecture that provides sustained hepatic functions for at least four weeks. In this poster abstract, we present a human hepatocyte co-cultures model using an integrated qualitative/quantitative high resolution mass spectrometry approach to assess metabolic stability using SWATH (Sequential Window acquisition of All Theoretical fragment ion spectra) for non-targeted MS/MS metabolite analysis. The assay was evaluated using propranolol, lorazepam, zoniporide, and ranitidine at clinically relevant concentration (1 µM) in 96-well format.

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