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Studies on Repository Compound Stability in DMSO under Various Conditions

xueheng.cheng{at}abbott.com

Jill Hochlowski

Hua Tang

Darlene Hepp

Carl Beckner

Stan Kantor

Robert Schmitt

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL.

The chemical stability of repository compounds is affected by various environmental conditions during long-term storage. Studies were carried out to evaluate the effects of the following potential causes of instability of compounds in DMSO at a 10-mM concentration: water, oxygen, freeze/thaw cycles, and storage container material. A set of compounds was selected for the study based on structural diversity and functional group representation. Compound concentration was determined with liquid chromatography/ultraviolet spectroscopy/mass spectrometry (LC/UV/MS) analysis relative to an internal standard added to each sample. An accelerated study was conducted, and results demonstrate that most compounds are stable for 15 weeks at 40 °C. Water is more important in causing compound loss than oxygen. The freeze/thaw cycle study was done with freezing at -15 °C and thawing under nitrogen atmosphere at 25 °C. Two methods were used to redissolve compounds after thawing: agitation and repeated aspiration/dispense. The results indicate no significant compound loss after 11 freeze/thaw cycles. Compound recovery was also measured from glass and polypropylene containers for 5 months at room temperature, and no significant difference was found for these 2 types of containers. (Journal of Biomolecular Screening 2003:292-304)

Key Words: DMSO • repository compound stability • high-throughput screening • compound decomposition • freeze/thaw • liquid chromatography/ultraviolet spectroscopy/mass spectrometry (LC/UV/MS)

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