Chen Zhi, Weber Stephen G
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Anal Chem. 2007 Feb 1;79(3):1043-9. doi: 10.1021/ac061649a.
A high-throughput method has been developed for lipophilicity measurement. It measures the partition coefficient of a solute between a polymer phase and an aqueous phase (Ppw) in a 96-well format. The polymer is plasticized poly(vinyl chloride) (PVC), which is widely used as a material for clinical containers and ion-selective electrodes. The composition is 2:1 (w/w) dioctyl sebacate and PVC. With six repeats, log Ppw values of 15 solutes have been determined in one 96-well microplate in 4 h. A linear relationship between log Ppw and log Pow (octanol-water partition coefficient) values exists with a correlation coefficient of 0.979. The slope and intercept of the log Ppw vs log Pow plot are statistically indistinguishable from 1 and 0, respectively. Similar to the HPLC method, by using the correlation line as a calibration curve, the measured log Ppw values can be used to predict log Pow. This protocol is faster than the HPLC method. Moreover, it is straightforward to extend the protocol to the determination of the distribution coefficient and pKa of charged solutes. We show that the log Ppw of the neutral form of racemic econazole is 4.83(+/-0.06), for the cationic form (presumably as a dihydrogen phosphate ion pair) 1.68(+/-0.04), and the pKa is 6.15(+/-0.04). This method has great flexibility as well and is potentially fully automated.
已开发出一种用于亲脂性测量的高通量方法。该方法以96孔板形式测量溶质在聚合物相和水相之间的分配系数（Ppw）。聚合物是增塑聚氯乙烯（PVC），它被广泛用作临床容器和离子选择电极的材料。其组成是2:1（w/w）癸二酸二辛酯和PVC。通过六次重复，在4小时内可在一个96孔微孔板中测定15种溶质的log Ppw值。log Ppw与log Pow（正辛醇-水分配系数）值之间存在线性关系，相关系数为0.979。log Ppw对log Pow图的斜率和截距在统计学上分别与1和0无显著差异。与高效液相色谱（HPLC）方法类似，通过将相关线用作校准曲线，测得的log Ppw值可用于预测log Pow。该方法比HPLC方法更快。此外，将该方法扩展到测定带电溶质的分配系数和pKa很简单。我们表明，外消旋益康唑中性形式的log Ppw为4.83（±0.06），阳离子形式（可能为磷酸二氢根离子对）的log Ppw为1.68（±0.04），pKa为6.15（±0.04）。该方法还具有很大的灵活性，并且有可能实现完全自动化。
