High-throughput purification of compound libraries

Abstract Synthesis of combinatorial libraries by parallel synthesis, followed by high- throughput biological screening, is the new paradigm for drug discovery. Purity of these libraries is an important consideration to obtain high-quality assay data. Liquid–liquid extraction and solid-phase capture reagents are useful in special cases for small numbers of compounds. However, for libraries of a few thousand compounds, HPLC is a viable alternative. Beyond these numbers, factors such as solvent requirements, the number of fractions and tracking become prohibitive. Supercritical fluid chromatography has been successfully employed in automated purification instrumentation and is expected to be capable of purifying libraries of tens-of-thousands of compounds.