High-throughput log P determination by MEEKC coupled with UV and MS detections

A high-throughput screening method using MEEKC was developed for the determination of 1-octanol-water partition coefficients (log P-oct) Two approaches were carried out to decrease determination times to about 20 min per compound. (i) a dynamically coated capillary was used to increase the EOF at low pH, allowing the measurement of log P-oct of acidic compounds and (ii) a short-end injection was performed to reduce the capillary effective length The analytical conditions were optimized to determine the lipophilicity of neutral, basic, and acidic compounds with log P, ranging from 0 to 5 The developed method was first applied to a well-balanced set of 35 reference compounds, and second to a set of 21 acidic and 29 basic pharmaceutical compounds. Finally, determinations were achieved with MS detection, allowing a 20-fold throughput increase thanks to sample pooling. An atmospheric pressure photoionization source was selected to advantageously replace ESI as it was less affected by the non-volatile BGE additives used in MEEKC