Methods for Measuring log P

In the Sirius pH-metric method, a weighed sample (typically 0.5 – 1.0 mg on SiriusT3 is dissolved in a two-phase water-octanol system, and titrated over a pH range (typically 2 to 12 for bases and ampholytes,

12 – 2 for acids). Although the solution becomes opaque during stirring, the pH electrode continues to measure pH of the aqueous component of the solution. Results are obtained by a complex computational process. The pH of each point in the titration curve is calculated using equations that contain pKa and P, and the calculated points are fitted to the measured curve by manipulating the P value. The value of P that provides the best fit is taken to be the measured P value, and is reported as the logarithm , i.e. log P.

As well as log P, the log D value as a function of pH is determined from the data.

In this example the log P of Lidocaine has been measured, with a result of 2.30.