Screening of octanol–water partition coefficients for pharmaceuticals by pressure-assisted microemulsion electrokinetic chromatography

A rapid screening assay for the determination of octanol–water partition coefficients (log Pow) of pharmaceuticals was developed by using pressure-assisted microemulsion electrokinetic chromatography (MEEKC). The microemulsion system contains 50 mM sodium dodecyl sulfate, 0.87 M 1-butanol, 82 mM heptane, and 50 mM borate–phosphate (2:3) at pH 10. Ten standard compounds with known log Pow values from −0.26 to 4.88 were used for constructing the calibration curve of log Pow against the MEEKC retention factor, log k. The log Pow 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 Pow 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 Pow screening of weakly basic, weakly acidic, and neutral pharmaceuticals with log Pow=0–5 and pKa≤10.