Accurate automated logPo/w measurement by gradient-flow liquid-liquid partition chromatography. Part 1. Neutral...

There is a continuing need for a method which can measure logPoctanol/water accurately and precisely. Liquid-liquid partition chromatography is ideally suited for this as the retention time is a direct function of the partition or distribution coefficient. However, the range of measurements using isocratic-flow conditions is limited by the log-linear relation between run time and logPo/w. The use of gradient-flow programming and short columns gives a more versatile procedure, so that appropriate data points can be collected at both the low and high ends of the chromatographic run, corresponding to logPo/w values between 1 and 4. At the same time the precision, accuracy and versatility of the method are kept. This study is a validation of the procedure and measures the logPo/w on 23 representative pharmaceuticals, comprising a mixed set of neutral compounds. The linear plot fitting micropartition logPo/w and those found in literature shows a slope close to unity and a residuum close to zero. This indicates that gradient-flow micropartition chromatography is ruled by partitioning between octanol and the aqueous phase.