Combinatorial Chemistry Libraries, Analysis of

Abstract

AbstractMany of the analytical techniques applied to the analysis of traditional pharmaceutical compounds are used to characterize combinatorial chemistry libraries. In both cases, the medicinal chemist is primarily concerned with verifying the identity and purity of the compounds synthesized. The identity of a compound usually is confirmed spectroscopically by Fourier transform infrared (FTIR) spectroscopy, mass spectrometry (MS), and/or nuclear magnetic resonance (NMR) spectroscopy, while purity is determined using a chromatographic technique, such as high‐performance liquid chromatography (HPLC). Combinatorial chemistry libraries may contain 100–100 000 compounds present as single species or as mixtures. The need to efficiently characterize such large numbers of compounds has been the primary motivation behind the development of many of the chromatographic–spectroscopic techniques applied to the analysis of combinatorial chemistry libraries. Many of these techniques have utility outside of the realm of normal library characterization. For example, the combination of affinity chromatography and MS has proven useful for screening combinatorial chemistry libraries against specific biological targets. The major impediments to the analysis of combinatorial chemistry libraries have been the challenges of designing analytical methods compatible with the wide chemical diversity of compounds encountered in these libraries, and the unique sample preparation and handling requirements imposed by combinatorial synthesis.