Potentiometric determination of octanol–water and liposome–water partition coefficients (log P) of ionizable organic compounds

The logarithm of the octanol–water partition coefficient, log P, is a key physicochemical property for both pharmaceutical drugs and agrochemicals. It is also required by legislation as part of the physicochemical properties profile for high volume production chemicals. This Letter describes a simple method for determining log P values (over a wide range from −0.8 to 5.3) for 12 organic weak acids and bases using potentiometric titrations, with octanol or phosphatidyl choline liposomes as the partitioning medium. Such titrations take comparatively little time (about 30–45 min per titration), are easy to implement, and can be carried out with an inexpensive laboratory titrator.