High-Throughput HPLC Method for the Measurement of Octanol-Water Partition Coefficients without an Organic Modifier.

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Computational Chemistry

Background:

• Accurate determination of octanol-water partition coefficients (logP) is crucial for drug discovery, agrochemical development, and chemical safety assessments.
• Traditional methods for logP determination can be time-consuming, require organic solvents, or lack applicability to ionizable compounds.
• Existing chromatographic methods may have limitations in the measurable logP range or require specific mobile phase additives.

Purpose of the Study:

• To develop and validate a high-performance chromatographic method for determining octanol-water partition coefficients (logP) of organic molecules.
• To establish a method suitable for a wide range of compounds, including those with acidic and basic pKa values.
• To create a robust and high-throughput analytical technique for industrial applications.

Main Methods:

• Utilized short-alkyl-chromatographic columns coated with octanol in the mobile phase.
• Employed a mobile phase without organic additives to measure logP values.
• Validated the method using a diverse set of 146 commercial molecules and over 27,000 proprietary research molecules.

Main Results:

• The method accurately measures logP values within the range of 0-5.6.
• The chromatographic method demonstrated high accuracy across a large dataset of diverse organic molecules.
• The method is insensitive to analyte concentration or purity, enhancing its reliability.

Conclusions:

• The developed chromatographic method offers an accurate, efficient, and versatile approach for logP determination.
• This technique is well-suited for the pharmaceutical, agrochemical, and fine chemical industries, supporting research and development.
• The generated data has been instrumental in training a machine learning model for predictive logP analysis.