June 5, 2005, ASMS 2005, San Antonio, TX, USA

Structure-Based LC/MS Method Development for High-Throughput Analyses

David S. Bell

Abstract

Generic or standard chromatographic methods have become a critical tool in high-throughput analysis, especially for LC/MS experiments. A limited number of chromatographic methods are designed such that sufficient resolution is obtained for the majority of anticipated samples. A favorite or most generic method is often utilized first; however, when this method provides unsuitable results, time-consuming reanalysis with secondary methods is required. An automated selection tool that enables the a priori prediction of the most suitable method would therefore greatly facilitate LC/MS analyses.

A limited number of generic methods have been designed to address the vast majority of drug-like compounds. Eight chromatographic methods were designed, 250 compounds were analyzed with each method, and the structures and retention data were assembled into a database. Innovative software was then utilized, in conjunction with the database, to provide retention time predictions for a wide variety of pharmaceutically-relevant analytes. The analyst inputs the structures for the expected analytes in the sample, and the software predicts the retention times for each analyte, for each separation method.

The prediction tool has been shown effective in retention time window prediction for a wide variety of pharmaceutical compounds via laboratory experimental validation. Significant coverage of pharmaceutical space has also been virtually verified. The resulting chromatographic methods in conjunction with method selection software constitute a system for accurate suitable method prediction for the vast majority of anticipated analytes, enabling facilitated high-throughput LC/MS analyses.

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Relevant Products: ACD/ChromGenius

Relevant Solution: Combinatorial and High-Throughput Chemists, Chromatography