Science

Log P Validations

The two-phase pH-metric titration method  that we use for log P 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 log P 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 log P values (typically between -1 and +6) because experiments can be run with widely different ratios of octanol to water volume.

Sirius-measured log P values feature in many publications, some of which are listed in our bibliography. Of these, the following were validation studies that compared our log P results with independently-measured log P 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 log P 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.

 

 

 

The measurement of log P on the SiriusT3 complies with the OECD Guideline for Testing of Chemicals – Partition Coefficient (n-octanol/water): pH-metric Method for Ionisable Substances. Draft Guideline 122. November 2000.