High-throughput purification of compound libraries

Synthesis of combinatorial libraries by parallel synthesis, followed by hig h-throughput biological screening, is the new paradigm for drug discovery. Purity of these libraries is an important consideration to obtain high-qual ity assay data. Liquid-liquid extraction and solid-phase capture reagents a re useful in special cases for small numbers of compounds. However, for lib raries of a few thousand compounds, HPLC is a viable alternative. Beyond th ese numbers, factors such as solvent requirements, the number of fractions and tracking become prohibitive. Supercritical fluid chromatography has bee n successfully employed in automated purification instrumentation and is ex pected to be capable of purifying libraries of tens-of-thousands of compoun ds.