Developments of a Fully Automated Parallel HPLC/Mass Spectrometry System for the Analytical Characterization and Preparative Purification of Combinatorial Libraries

Abstract

An automated parallel analytical/preparative HPLC/MS workstation has been developed to increase the analysis speed for characterizing and purifying combinatorial libraries. The system incorporates two columns operated in parallel for both LC/MS analysis and preparative LC/MS purifications (a technique we have named “parallel Analyt/PrepLCMS”). Keys to the successful development of this system have been the design of a multiple sprayer IonSpray interface to support flows from multiple columns and the design of a valving configuration which is under complete software control for delivering the crude samples to the two HPLC columns from a single autosampler. In comparison with the conventional LC/MS systems, where compounds are analyzed sequentially (i.e., one at a time), our parallel Analyt/PrepLCMS system provides an important increase in sample throughput, especially critical in the field of combinatorial chemistry, where compound libraries are generated frequently in parallel arrays and require high-thro...