Metabolic Stability Assay Using Human Hepatocyte Co-cultures and Integrated Qualitative/Quantitative High Resolution Mass Spectrometry
Poster Sep 08, 2014
Alex Zang, Ragu Ramanathan, Cornelia Smith, Caroline Lee, Helen Shen, and Zamas Lam
Traditional metabolic stability methodology using suspended hepatocyte for drug candidates screening is limited 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 weeks1. In this presentation, we investigated human hepatocyte co-cultures model using an integrated qualitative/quantitative high resolution mass spectrometry approach to assess metabolic stability using TOF-MS and Sequential Window Acquisition of All THeoretical fragment ion spectra (SWATH) for non-targeted metabolite MS/MS analysis. The assay was evaluated using propranolol, lorazepam, ranitidine, and zoniporide, at clinically relevant concentration (1 μM) in 96-well format.