Stability of screening compounds in wet DMSO

Area of Science:

• Medicinal Chemistry
• Analytical Chemistry
• Chemical Biology

Background:

• Compound stability and solubility are critical in drug discovery.
• Storage conditions, particularly solvent composition, significantly impact compound integrity.
• DMSO/water mixtures are increasingly used but their long-term effects require thorough investigation.

Purpose of the Study:

• To assess the stability of compounds stored in a DMSO/water (90/10) mixture.
• To validate Novartis's storage concept using a DMSO/water solvent system.
• To evaluate the impact of water content in DMSO stocks on compound purity over time.

Main Methods:

• Monitoring the purity of 1404 diverse compounds over several months.
• Utilizing analytical techniques to assess compound integrity in wet DMSO.
• Collecting purity data during the chemical validation of high-throughput screening actives.

Main Results:

• 85% of tested compounds remained stable in wet DMSO over a 2-year period at 4°C.
• The study demonstrated the feasibility and reliability of the Novartis storage concept.
• Purity data provided insights into improving analytical quality for screening decks.

Conclusions:

• The DMSO/water (90/10) storage concept is a pragmatic and effective approach for compound management.
• This method balances the benefits of DMSO/water mixtures with minimized disadvantages for compound stability.
• The findings support the optimization of analytical quality for high-throughput screening by leveraging purity data.