An automated system for the purification of combinatorial libraries by preparative LC/MS

Abstract

The emergence of combinatorial chemistry and parallel synthesis techniques in pharmaceutical research has created the need for effective sample purification techniques. High-performance liquid chromatography (HPLC) and mass spectrometry are well suited to determining sample identity and purity on an analytical scale. These technologies also may be applied to design systems for purifying combinatorial arrays. This article describes an automated purification system based on a stand-alone preparative HPLC and fraction collector. Purification of a combinatorial array is performed in two steps. First, the array samples are characterized by liquid chromatography and atmospheric pressure chemical ionization mass spectrometry (APcI MS) on an analytical scale. These analytical data are used to guide the subsequent purification of the combinatorial array by preparative HPLC with UV detection alone. The purification system is composed of modular, low-cost components and requires little operator training. Reversed-phase, normal-phase, and chiral chromatographic methods have been used with the system to isolate milligram quantities of chromatographically pure material from combinatorial libraries. © 1997 John Wiley & Sons, Inc. Lab Robotics and Automation 9: 309–321, 1997