DETERMINATION OF TRUE OCTANOL WATER PARTITION-COEFFICIENTS BY MEANS OF SOLVENT GENERATED LIQUID-LIQUID CHROMATOGRAPHY

Compared to other methods for the determination of octanol-water parti tion coefficients chromatography offers a number of advantages: sample purification is unnecessary, the partition coefficients of the compon ents of a mixture can be measured simultaneously and a minimum amount of sample is needed. In the past these determinations were almost excl usively carried out by liquid-solid chromatography (LSC) on alkyl bond ed silica as stationary phase (conventionally described as 'reversed-p hase liquid chromatography; RPLC). Such systems based on liquid-solid distribution are, however, a poor simulation of liquid-liquid partitio n. On the other hand liquid-liquid chromatographic columns loaded with high amounts of water-saturated octanol are unstable since they suffe r from ''column bleeding'' - a loss of the stationary liquid octanol p hase caused by erosion. It is shown that the technique of solvent gene rated liquid-liquid chromatography (SGLLC) leads to stable columns wit h liquid-liquid partition as the predominant retention mechanism, if s ystematic 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 scat tering of the retention data of calibration standards around the calib ration line. The use of SGLLC thus significantly improves the accuracy and precision of the resulting octanol-water partition coefficients.