UPLC with Rapid MS Data Acquisition and Automated MS/MS Development to Enhance the Throughput of Drug Discovery ADME Screening

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Amy E. Davies, Ed Sprake
Pharmaceutical Sciences World Congress, April 25 - 27, Amsterdam, The Netherlands
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In vitro microsomal stability is a screening assay used to predict Phase I metabolism of early drug candidates. This assay is often incorporated into the early discovery stage of drug development to aid rapid elimination of compounds that posses unfavorable ADME characteristics. Robotic instrumentation has greatly improved the sample preparation throughput of this assay meaning large numbers of samples can be rapidly prepared  with relative ease. A consequence of this is the assay bottleneck has moved to the sample analysis stage and vast numbers of structurally diverse analytes must be rapidly optimized for their LC/MS/MS detection. This work describes the application of Ultra Performance® Liquid Chromatography (UPLC) with rapid MS/MS data acquisition together with QuanOptimise Application Manager(TM) software to automate the process of sample optimisation and analysis as well as increase the analytical throughput of a microsomal stability assay.

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