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This version was published on February 1, 2006
Journal of Biomolecular Screening, Vol. 11, No. 1, 40-47 (2006)
DOI: 10.1177/1087057105281363

Development and Application of an Automated Solution Stability Assay for Drug Discovery

Li Di

P.O. Box CN 8000, Princeton, NJ 08543-8000 dil{at}wyeth.com

Edward H. Kerns

Hong Chen

Susan L. Petusky

Screening of solution stability provides an early alert on potential liabilities of drug candidates so that strategies can be developed to overcome the challenges. Afully automated solution stability assay has been developed to accelerate traditionalmanual operation. The assay uses the advanced capabilities of a high-performance liquid chromatography instrument that is present in many pharmaceutical research laboratories. The samples are prepared automatically by a temperature-controlled autosampler. The samples are delivered to the stability matrices, mixed, incubated, and injected at selected time points during the reaction time course. This automated process occurs without operator intervention, thus allowing 96 experiments to be run with0.5hof a scientist's time compared to 8 h for the same studywhenperformedmanually. Automationnotonly eliminates themanual operation but also improves accuracy and throughput. The assay protocol has been optimized to achieve homogenous mixing and eliminate carryover. The assay is robust, flexible, and high throughput. It can be used to study stability for a large number of samples undermultiple incubation conditions and has awide range of applications in drug discovery and development, such as screening compound stability in biological assaymedia, obtaining a stability-pH profile, surveying compound stability in physiological fluids, and performing development forced degradation and excipient compatibility.

Key Words: stability • automation • high throughput • stability-pH profile • hydrolysis • chemical stability • HPLC • LC-MS • kinetics


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