Degim T, Zaimoglu V, Akay C, Degim Z
University of Gazi, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey.
Farmaco. 2001 Sep;56(9):659-63. doi: 10.1016/s0014-827x(01)01114-4.
The octanol/water partition coefficient (log K) is one of the most commonly used parameters in structure-activity relationships in many areas such as drug design (including pesticides), pharmacokinetics, anesthesiology, environmental sciences, toxicology, bioaccumulation and predicting skin permeability as a predictive parameter. log K is generally determined using shake flask method, but the possibility of calculating log K using pH-metric titrations and half neutralization points is demonstrated in this study. The potentiometric pH titration technique has been developed as an automatic technique for log K determination but it can be achieved by manual titrations. This technique uses the pKa of the substance. The pKa of the substance shifts pK'a when the titration is repeated in the presence of octanol. log K value of the substance can be determined using pKa, pK'a values and relevant equation. The aim of the study was to determine the log K values of a series of compounds using pH-metric titrations and to compare pH-metric log K determination results with the other methods. The log K values of famotidine, naproxen, nizatidine, ranitidine and salicylic acid were determined using both shake flask method and potentiometric titrations. Their log K values were also calculated theoretically using computer program and all results were compared. The pH-metric log K values were found to be close to the shake flask method results. This method was found to be useful for the determination of log K values as it provides a high degree of accuracy even in the presence of titratable impurities in the solution.
正辛醇/水分配系数（log K）是药物设计（包括农药）、药代动力学、麻醉学、环境科学、毒理学、生物累积以及预测皮肤渗透性等许多领域中结构-活性关系最常用的参数之一，作为一个预测参数。log K通常采用摇瓶法测定，但本研究证明了使用pH滴定法和半中和点计算log K的可能性。电位pH滴定技术已发展成为一种测定log K的自动技术，但也可以通过手动滴定实现。该技术利用物质的pKa。当在正辛醇存在下重复滴定时，物质的pKa会转变为pK'a。物质的log K值可以使用pKa、pK'a值和相关方程来确定。本研究的目的是使用pH滴定法测定一系列化合物的log K值，并将pH滴定法测定log K的结果与其他方法进行比较。使用摇瓶法和电位滴定法测定了法莫替丁、萘普生、尼扎替丁、雷尼替丁和水杨酸的log K值。还使用计算机程序从理论上计算了它们的log K值，并对所有结果进行了比较。发现pH滴定法测定的log K值与摇瓶法的结果相近。该方法被发现对于测定log K值很有用，因为即使溶液中存在可滴定杂质，它也能提供高度的准确性。
