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 m M sodium dodecyl sulfate, 0.87 M 1-butanol, 82 m M heptane, and 50 m M 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 p K a ≤10.