The two-phase pH-metric titration method that we use for logP was first described in 1952 (Dyrssen, D. Sven. Kem. Tidskr., 1952, 64, 213-224). At that time calculations were difficult, but the advent of computers now makes it a feasible method for routine use.
The pH-metric method is a good choice for measuring logP of ionisable compounds because only one experiment is required to produce a profile of lipophilicity vs. pH (plus an experiment to measure the pKa). To cover the pH range, other methods would require results measured in several different buffer-octanol systems. The pH-metric method can measure a wide range of logP values (typically between -1 and +6) because experiments can be run with widely different ratios of octanol to water volume.
Pion-measured logP values feature in many publications, some of which are listed in our bibliography. Of these, the following were validation studies that compared our logP results with independently-measured logP values:
26 compounds compared: Slater, B.; McCormack, A.; Avdeef, A.; Comer, J. pH-Metric logP. 4. Comparison of Partition Coefficients Determined by Shake-Flask, HPLC and Potentiometric Methods. J. Pharm. Sci 1994, 83, 1280-1283.
18 compounds compared: Comer, J.; Chamberlain, K. A.; Evans, A.; Validation of pH-metric technique for measurement of pKa and logPow of ionizable herbicides. SAR QSAR Environ. Res., 1995, 3 (4), 307-313.
23 compounds compared: Takács-Novák, K.; Avdeef, A.; Interlaboratory study of logP determination by shake-flask and potentiometric methods. J. Pharm. Biomed. Anal. 1996, 14, 1405-141
Results from these three studies are compared in the graph below.