Method Development and Application of an Accelerated Solution Stability Screen for Drug Discovery

Area of Science:

• Drug discovery and development
• Analytical chemistry
• Chemical stability assessment

Background:

• Assessing the solution stability of experimental molecules is critical in drug discovery to avoid attributing effects to degradation products.
• Early identification of compound degradation pathways is essential for successful drug development.

Purpose of the Study:

• To describe improvements and application of a streamlined, higher-throughput method for testing solution stability.
• To incorporate mass spectrometry for the identification of degradation products.
• To reduce the amount of compound needed for stability assays.

Main Methods:

• Development of a higher-throughput solution stability assay.
• Utilizing 10 mM dimethyl sulfoxide (DMSO) solutions to minimize compound usage.
• Employing mass spectrometry detection for degradation product identification.
• Assessing compound stability across a range of pH, oxidizing, and reducing conditions.

Main Results:

• Demonstration of a streamlined, high-throughput method for solution stability testing.
• Successful identification of degradation products using mass spectrometry.
• Validation of the assay with a set of marketed drugs to illustrate its application.

Conclusions:

• The presented method offers a robust and efficient approach for evaluating compound solution stability early in the drug discovery process.
• This high-throughput screen aids in identifying potential liabilities and guiding the selection of stable drug candidates.