Stability of Screening Compounds in Wet DMSO

• Published in: Journal of biomolecular screening Vol. 13; no. 10; pp. 999 - 1006
• Main Authors: Engeloch, Caroline, Schopfer, Ulrich, Muckenschnabel, Ingo, Le Goff, Francois, Mees, Hervé, Boesch, Karoline, Popov, Maxim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2008
• Subjects: Chromatography, Liquid; compound management; Dimethyl Sulfoxide - chemistry; Drug Stability; high-throughput liquid chromatography/mass spectroscopy (HT LC/MS); Mass Spectrometry; quality control (QC); Small Molecule Libraries - chemistry; Small Molecule Libraries - isolation & purification; Software; storage conditions; Ultraviolet Rays; Water - chemistry; wet DMSO; wet DMSO; storage conditions; high-throughput liquid chromatography/mass spectroscopy (HT LC/MS); compound management; quality control (QC)
• ISSN: 2472-5552; 1087-0571; 2472-5560
• DOI: 10.1177/1087057108326536

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.