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P1005
An Automated LC/MS/MS Protocol To Enhance Throughput of Physico-Chemical Property Profiling In Drug Discovery
Presenter Darcy Shave, Waters Corporation, USA
Additional Authors: Peter G. Alden, Kate Yu, Rob Plumb, Warren Potts
The synthesis of large, focused chemical libraries allows pharmaceutical companies to rapidly screen large numbers of compounds against disease targets.  Active compounds resulting from these screens are traditionally ranked based on their activity, binding and/or specificity.  Turning these hits into leads requires further analysis and optimization of the compounds based upon their physicochemical and ADME characteristics. The critical factor to consider in physicochemical profiling is throughput. The bottlenecks to throughput include MS method optimization for a large variety of compounds and data management for the large volume of data generated.Currently, experiments including solubility, chemical and biological stability, water/octanol partitioning, PAMPA, Caco-2, and protein binding are used to generate physicochemical profiles of compounds in drug discovery.  The measurement of physicochemical properties from these studies is easily enabled using chromatographic separation and quantitation using LC/MS/MS/UV.  While the sample analyses may be efficient, the processing of the data and the interpretation of the results often requires tedious and time-consuming manual manipulation and calculation.This paper describes an approach to solving these problems by the use of a novel software package that allows for the design of experiments, data acquisition, and the processing as well as report generation in a fully automated manner.To demonstrate the usage of this software package we have developed an automated UPLC/MS/MS protocol for data generation.  The data acquired from multiple assays were processed by a single processing method, all in an automated fashion. As a result, the physicochemical profiling process was significantly simplified and throughput increased.