title: Investigation of 3 industry-wide applied storage conditions for compound libraries.
abstract: 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 degrees C, (2) under argon at -20 degrees C, and (3) under ambient atmosphere at -20 degrees 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 degrees C under argon, a loss of 21% for storage at -20 degrees C under ambient atmosphere, and a strong decrease of 58% for storage at +15 degrees 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.
authors.affiliation: Evotec AG, Hamburg, Germany.
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Ilouga
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Christian
authors.initials: C
authors.lastname: Kirchhoff
authors.forename: Bernd
authors.initials: B
authors.lastname: Schierholz
authors.forename: Julian
authors.initials: J
authors.lastname: Wölcke
mesh_terms: D016001:Confidence Intervals; D004345:Drug Industry; D004356:Drug Storage / Q000379:methods* / Q000706:statistics & numerical data; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D012984:Software; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations