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Stability of Screening Compounds in Wet DMSO

Lead Finding Platform/Novartis Compound Archive, Novartis Institutes for BioMedical Research, Basel, Switzerland, Caroline.Engeloch{at}novartis.com

Ulrich Schopfer

Lead Finding Platform/Novartis Compound Archive, Novartis Institutes for BioMedical Research, Basel, Switzerland

Ingo Muckenschnabel

Analytical Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland

Francois Le Goff

Analytical Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland

Hervé Mees

Lead Finding Platform/Novartis Compound Archive, Novartis Institutes for BioMedical Research, Basel, Switzerland

Karoline Boesch

Lead Finding Platform/Novartis Compound Archive, Novartis Institutes for BioMedical Research, Basel, Switzerland

Maxim Popov

Lead Finding Platform/Molecular and Library Informatics, Novartis Institutes for BioMedical Research, Basel, Switzerland

The impact of storage conditions on compound stability and compound solubility has been debated intensely over the past 5 years. At Novartis, the authors decided to opt for a storage concept that can be considered controversial because they are using a DMSO/water (90/10) mixture as standard solvent. To assess the effect of water in DMSO stocks on compound stability, the authors monitored the purity of a subset of 1404 compounds from ongoing medicinal chemistry projects over several months. The study demonstrated that 85% of the compounds were stable in wet DMSO over a 2-year period at 4 °C. This result validates the storage concept developed at Novartis as a pragmatic approach that takes advantage of the benefits of DMSO/water mixtures while mediating the disadvantages. In addition, the authors describe how purity data collected over the course of the chemical validation of high-throughput screening actives are used to improve the analytical quality of the Novartis screening deck. (Journal of Biomolecular Screening 2008:999-1006)

Key Words: compound management • storage conditions • wet DMSO • high-throughput liquid chromatography/mass spectroscopy (HT LC/MS) • quality control (QC)

This version was published on December 1, 2008

Journal of Biomolecular Screening, Vol. 13, No. 10, 999-1006 (2008)
DOI: 10.1177/1087057108326536


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