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 Poct). 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 Poct 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 Poct 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.