Determination of true octanol-water partition coefficients by means of solvent generated liquid-liquid chromatography

Abstract

Compared to other methods for the determination of octanol-water partition coefficients chromatography offers a number of advantages: sample purification is unnecessary, the partition coefficients of the components of a mixture can be measured simultaneously and a minimum amount of sample is needed. In the past these determinations were almost exclusively carried out by liquid-solid chromatography (LSC) on alkyl bonded silica as stationary phase (conventionally described as ‘reversed-phase liquid chromatography; RPLC). Such systems based on liquid-solid distribution are, however, a poor simulation of liquid-liquid partition. On the other hand liquid-liquid chromatographic columns loaded with high amounts of water-saturated octanol are unstable since they suffer from “column bleeding” — a loss of the stationary liquid octanol phase caused by erosion. It is shown that the technique of solvent generated liquid-liquid chromatography (SGLLC) leads to stable columns with liquid-liquid partition as the predominant retention mechanism, if systematic errors due to specific adsorption effects are avoided by the selection of an “inert” solid support. This is demonstrated by the comparison of LSC and SGLLC data. SGLLC significantly reduces the scattering of the retention data of calibration standards around the calibration line. The use of SGLLC thus significantly improves the accuracy and precision of the resulting octanol-water partition coefficients.