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. 2011 Sep 9;2(8):680–688. doi: 10.1007/s13238-011-1086-2

Driving efficiency in a high-throughput metabolic stability assay through a generic high-resolution accurate mass method and automated data mining

Wenqing Shui 1,2,✉, Song Lin 3, Allen Zhang 4, Yan Chen 4, Yingying Huang 4, Mark Sanders 4
PMCID: PMC4875332  PMID: 21904983

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1086-2 and is accessible for authorized users.

Keywords: metabolic stability, high-resolution mass spectrometry, accurate mass, ultra-high performance liquid chromatography

Electronic supplementary material

13238_2011_1086_MOESM1_ESM.xls (44.5KB, xls)

Supplementary material, approximately 44.5 KB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1086-2 and is accessible for authorized users.

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Supplementary Materials

13238_2011_1086_MOESM1_ESM.xls (44.5KB, xls)

Supplementary material, approximately 44.5 KB.

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