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Automated Liquid-Liquid Extraction and Ion-Exchange Solid-Phase Extraction for Initial Purification

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The development of combinatorial chemistry has made a profound impact on the pharmaceutical industry by producing a large number of structurally diverse compounds in a very short amount of time. Combined with high-throughput screening, bioinformatics, and laboratory automation, the combinatorial chemistry approach has led to a significantly accelerated drug discovery process compared to a traditional one-compound-at-a-time approach (1 ). With a potential explosion of the number of biological targets available for various diseases from genomics and proteomics, combinatorial chemistry and parallel synthesis will be further embraced by the pharmaceutical industry, leading the way to rapidly generate a large number of chemical libraries to screen for different disease targets. Currently, thousands of potentially bioactive compounds are made every week by combinatorial chemistry synthesis. Subsequently, these compounds go through various high-throughput biological screens in different therapeutic areas to find biologically active compounds or hits. However, in order to ensure true hits from these various screening assays, initial sample purification to remove assay-interfering components is required to prevent false positive or negative results. This initial sample cleanup step poses a great challenge to synthetic and analytical chemists, because purification in a high-throughput and fully automated fashion is needed to keep up with the fast pace of combinatorial synthesis and high-throughput biological screening.
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