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Investigation of 3 Industry-Wide Applied Storage Conditions for Compound Libraries

Dirk Winkler

Christian Kirchhoff

Bernd Schierholz

Evotec AG, Hamburg, Germany

Julian Wölcke

Novartis Institutes for Biomedical Research, Basel, Switzerland

The appropriate storage conditions for a compound file are a crucial factor for the success of drug discovery projects. In this study, 778 highly diverse compounds dissolved in 100% DMSO were stored under 3 industry-wide accepted storage conditions, and the compound integrity was monitored for a period of 6 months. The storage conditions selected were (1) under argon at +15 °C, (2) under argon at -20 °C, and (3) under ambient atmosphere at -20 °C. Each sample was assessed every 4 weeks by liquid chromatography coupled to mass spectrometry (LC/MS). Based on the resulting experimental data, a statistical projection of compound integrity over a period of 4 years for each of the 3 storage conditions was generated applying a linear mixed-effects model. A moderate loss of compound integrity of 12% was calculated for storage at -20 °C under argon, a loss of 21% for storage at -20 °C under ambient atmosphere, and a strong decrease of 58% for storage at +15 °C under argon over this period. The initial purity of the compounds does also influence the rate of compound degradation. Compounds with an initial purity of 50% to 75% degraded faster than compounds with an initial purity of more than 75%. The results of the study enable the prediction of the point in time, when the purity of a compound population falls below a predefined threshold that would trigger the resolubilization or retirement of the compound population represented by the analyzed samples.

Key Words: drug discovery • compound integrity • compound storage • liquid chromatography coupled to mass spectrometry (LC/MS) • high-throughput screening (HTS) • linear mixed-effects model

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