title: Integration of a rapid automated solubility classification into early validation of hits obtained by high throughput screening.
abstract: Besides the structural verification of hits generated by high throughput screening also the determination of physicochemical properties is essential for an efficient lead identification. Especially solubility is fundamental for the correct planning and interpretation of experiments. We describe the set up of a fast automated solubility test within our existing workflow for hit validation to assure compound identity and purity. 384-Well plates with hit validation compound solution are used for analysis employing liquid chromatography and mass spectrometry (LC/MS). The remaining compound solution was used for a fast automated solubility classification employing a nephelometer integrated into a Tecan robotic workstation. Thereby 9000 compounds were classified as poorly- and well-soluble. This rapid and simple test does not require any additional amount of sample or sample processing than before but provides additional information on the hits at an early stage of lead identification. Validated by a more detailed nephelometric analysis for 500 out of the 9000 compounds in different buffer systems this simple test has shown to produce relevant data.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Research, Lead Discovery Analytics, Birkendorfer Str. 65, 88397 Biberach, Germany. thilo.fligge@bc.boehringer-ingelheim.com
authors.forename: Thilo A
authors.initials: TA
authors.lastname: Fligge
authors.forename: Andrea
authors.initials: A
authors.lastname: Schuler
mesh_terms: D001331:Automation; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D013058:Mass Spectrometry; D008832:Microchemistry; D009391:Nephelometry and Turbidimetry / Q000295:instrumentation / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000145:classification*; D015203:Reproducibility of Results; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations