title: Screening of octanol-water partition coefficients for pharmaceuticals by pressure-assisted microemulsion electrokinetic chromatography.
abstract: A rapid screening assay for the determination of octanol-water partition coefficients (log P(OW)) of pharmaceuticals was developed by using pressure-assisted microemulsion electrokinetic chromatography (MEEKC). The microemulsion system contains 50 mM sodium dodecyl sulfate, 0.87 M l-butanol, 82 mM heptane, and 50 mM borate-phosphate (2:3) at pH 10. Ten standard compounds with known log P(OW) values from -0.26 to 4.88 were used for constructing the calibration curve of log P(OW) against the MEEKC retention factor, log k. The log P(OW) values of the compounds were calculated based on the log k values measured by MEEKC and the slope and intercept of the calibration curve. For 13 literature and 32 Roche compounds, about 90% of the log P(OW) values measured by MEEKC are within 0.5 log units of the values from the literature and potentiometric titration. The throughput is about 2 samples/h using +20 kV voltage plus 5 mbar air pressure for separation. This MEEKC method is applicable for log P(OW) screening of weakly basic, weakly acidic, and neutral pharmaceuticals with log P(OW) = 0-5 and pKa < or = 10.
authors.affiliation: Department of Pharmaceutics, Roche Palo Alto LLC, 3431 Hillview Avenue, R1-3 Palo Alto, CA 94304, USA. zhongjiang.jia@roche.com
authors.forename: Zhongjiang
authors.initials: Z
authors.lastname: Jia
authors.forename: Lijie
authors.initials: L
authors.lastname: Mei
authors.forename: Fangling
authors.initials: F
authors.lastname: Lin
authors.forename: Sujuan
authors.initials: S
authors.lastname: Huang
authors.forename: Robert B
authors.initials: RB
authors.lastname: Killion
mesh_terms: D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D000442:Octanols / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011312:Pressure; D014867:Water / Q000737:chemistry*
chemical_list: D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water