Mechanized determination of n-octanol/water partition constants using liquid—liquid segmented flow extraction

Abstract

A simple and rapid method for the determination of partition constants in the n-octanol/water system is presented. The substance under study is dissolved in n-octanol or water, and injected into a stream of the corresponding phase. Liquid-liquid segmented flow is utilized for equilibration of the two phases and after equilibration a fraction of the aqueous phase is separated with the aid of a hydrophilic membrane. The amount of substance in the aqueous phase is measured spectrophotometrically. The measurements are repeated at a small number of different phase flow ratios and the results obtained are plotted against these ratios. From slope and intercept for the regression line through these points the conditional partition constant, D', can be calculated. A simplified procedure using only two measurements, one of which is obtained with the flow rate of organic phase set to 0, can also be used. Partition constants in the range 0.48 < D < 873 (-0.32 < log D < 2.94) have been determined using this system. The precision, measured as relative standard deviation (RSD) is below 15%, corresponding to a standard deviation of +/- 0.1 log unit or less over the range of measurement. Measured values correspond to literature values within 0.07 log units. The time needed for a determination is about 15 min per substance, in many cases even shorter and the sample consumption is, in most cases, less than 1 mg.