title: High-throughput log P determination by MEEKC coupled with UV and MS detections.
abstract: 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(oct) 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.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet, Geneva, Switzerland.
authors.forename: Yveline
authors.initials: Y
authors.lastname: Henchoz
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Romand
authors.forename: Julie
authors.initials: J
authors.lastname: Schappler
authors.forename: Serge
authors.initials: S
authors.lastname: Rudaz
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
mesh_terms: D002138:Calibration; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D004655:Emulsions / Q000737:chemistry*; D016018:Least-Squares Analysis; D013058:Mass Spectrometry / Q000379:methods*; D009930:Organic Chemicals / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D004655:Emulsions; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012997:Solvents