Stability of screening compounds in wet DMSO

J Biomol Screen. 2008 Dec;13(10):999-1006. doi: 10.1177/1087057108326536. Epub 2008 Nov 21.

Abstract

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 degrees 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.

MeSH terms

  • Chromatography, Liquid
  • Dimethyl Sulfoxide / chemistry*
  • Drug Stability*
  • Mass Spectrometry
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / isolation & purification
  • Software
  • Ultraviolet Rays
  • Water / chemistry*

Substances

  • Small Molecule Libraries
  • Water
  • Dimethyl Sulfoxide