Slater B, McCormack A, Avdeef A, Comer J E
Rhône-Poulenc Rorer, Dagenham Research Centre, Essex, U.K.
J Pharm Sci. 1994 Sep;83(9):1280-3. doi: 10.1002/jps.2600830918.
The pKa and log P of 20 compounds, including six substituted phenols, two substituted quinolines, N-methylaniline, five barbiturate derivatives, two phenothiazines, and several other molecules of pharmaceutical interest, were determined by the potentiometric technique at 25 degrees C and ionic strength 0.1 M (KNO3). The log P values were determined also by partition HPLC. Three of the substances were of very low aqueous solubility, and for these the aqueous pKas were determined by extrapolation from methanol-water solutions using the Yasuda-Shedlovsky technique. Values of log P obtained both by potentiometry and by partition HPLC, which ranged from 0.3 to 5.4, were in very good acordance with literature values. The general applicability of the potentiometric technique to ionizable compounds of diversely varied structures was demonstrated by the study.
采用电位滴定法在25℃和离子强度0.1M(硝酸钾)条件下测定了20种化合物的pKa和log P值,这些化合物包括6种取代酚、2种取代喹啉、N-甲基苯胺、5种巴比妥酸盐衍生物、2种吩噻嗪以及其他几种具有药物活性的分子。log P值也通过分配高效液相色谱法进行了测定。其中3种物质的水溶性极低,对于这些物质,采用安田-谢德洛夫斯基技术从甲醇-水溶液中通过外推法测定了其水相pKa。通过电位滴定法和分配高效液相色谱法获得的log P值范围为0.3至5.4,与文献值非常吻合。该研究证明了电位滴定法对结构多样的可电离化合物具有普遍适用性。