title: Driving efficiency in a high-throughput metabolic stability assay through a generic high-resolution accurate mass method and automated data mining.
abstract: Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery. For drug candidate screening, it is common practice to use ultra-high performance liquid chromatography (U-HPLC) coupled with triple quadrupole mass spectrometry. This approach certainly results in short analytical run time; however, in assessing the true throughput, all aspects of the workflow needs to be considered, including instrument optimization and the necessity to re-run samples when information is missed. Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency. In addition, as the data is acquired in a non-biased manner, high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.
authors: College of Life Sciences, Nankai University, Tianjin 300071, China. angelshui@nankai.edu.cn
authors: Wenqing
authors: W
authors: Shui
authors: Song
authors: S
authors: Lin
authors: Allen
authors: A
authors: Zhang
authors: Yan
authors: Y
authors: Chen
authors: Yingying
authors: Y
authors: Huang
authors: Mark
authors: M
authors: Sanders
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057225:Data Mining; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism