Parallel preparative high‐performance liquid chromatography with on‐line molecular mass characterization

Abstract

High-throughput chemistry (HTC) is now an integral part of the lead discovery process in many pharmaceutical and related chemical companies. As this process becomes refined or improved, with the integration of systems with enhanced capabilities, and the requirement for quality compounds of high purity increases, purification is often considered a bottleneck. Although a wide range of purification techniques is available, high-performance liquid chromatography (HPLC) is usually the preferred method of purification to produce high-purity compounds. Parallel preparative HPLC with robust UV-guided fraction collection has been shown to reduce the bottleneck and complement the parallel synthesis systems. However, despite the success of this technique, post-purification analysis of fractions to identify the target compound adds an additional level of complexity. This paper describes the interfacing of the Biotage Parallex with the MUX interface on a single quadrupole mass spectrometer, thus combining robust UV-guided fractionation with on-line MS characterization.