Stability of screening compounds in wet DMSO.
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.
Engeloch
Caroline
C
Novartis Institutes for BioMedical Research, Basel, Switzerland. Caroline.Engeloch@novartis.com
Schopfer
Ulrich
U
Muckenschnabel
Ingo
I
Le Goff
Francois
F
Mees
Hervé
H
Boesch
Karoline
K
Popov
Maxim
M
D002853:Chromatography, Liquid; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D004355:Drug Stability; D013058:Mass Spectrometry; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000302:isolation & purification; D012984:Software; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry*
D054852:Small Molecule Libraries; D014867:Water; D004121:Dimethyl Sulfoxide