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Application of the Agilent Automated Purification Software in Highthroughput preparative HPLC-MS purification workflow of Libraries within the European Lead Factory Raquel Ortegaa, Martyna Bielskaa, Xenia Iwanowaa, Anna Karawajczyk b Danny van Oevelenc, Andreas Teic aLibrary Purification Department. bComputational Chemistry. Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Str. 76a, 44227 Dortmund, Germany. email: [email protected] cAgilent Technologies R&D and Marketing GmbH &Co KG; Hewlett-Packard Str. 8, 76337 Waldbronn, Germany. email: [email protected] The European Lead Factory is a collaborative public-private partnership established in 2013 aiming to deliver over 500 000 innovative drug discovery starting points in order to enhance the chances to find new valuable lead candidates that could result in the development of novel treatment options for patientsi. Taros Chemicals, a privately owned CRO company, is contributing with over 10 000 compounds per year into the Joint European Compound Collection (JECL). Within this poster we present a user friendly and highly efficient purification workflow based on Agilent OpenLAB CDS Automated Purification Software. The software has been developed by Agilent Technologies in a close collaborative project with Taros creating automated purification workflows based on reversed phase high performance liquid chromatography (HPLC) and mass spectrometry (MS). The system is suitable for a smart combination of UV- and mass-based fraction triggering and the automated transfer of data between each single process step (cross platform data transfer, scalability from analytic to preparative and automated transfer of fraction information to the pooling station) streamlining the workflow for highest productivity as the purification of crude products is usually the most time consuming part of organic compound preparationii. The results of the addressed library purification demonstrate a successful automated workflow. Two main challenges were accomplished: i) the detection and purification of low UV absorbance compounds and ii) chromatographic challenges due to the diversity of the physico-chemical properties –in this case 5 reaction types were performed in the last diversification point– including broad versatility of molecular properties within one scaffold. The efficiency of method development, speed of the purification and reduction of the costs are established with high values of recovery rates, purity and number of the final isolated compounds. The information recovered from the entire process has an intrinsic value in the design, synthesis and purification of future libraries. i ii Karawajczyk, A. et al. Drug Discovery Today 2015 (20) 11, 1310-1316. Cork, D. et al. Drug Discovery Today 2002 (7), 56-63.
