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

Abstract

We present a high-performance chromatographic method for the determination of octanol–water partition coefficients of organic molecules, suitable for pharmaceuticals, agrochemicals, and fine-chemicals featuring acidic and basic pK_a values. By selecting short-alkyl-columns based on length and coating them with octanol present in the mobile phase, we can measure a logP range of 0–5.6 without the use of an organic additive. The method has shown to be accurate for a set of 146 commercial molecules reported here, as well as over 27,000 in-house proprietary research molecules, the results of which have been used to train our own machine learning model. The method is also insensitive to analyte concentration or purity, and can be partially automated to obtain a relatively high throughput for industrial purposes.