pK Determination of Sparingly Soluble Compounds by Difference Potentiometry

Abstract

A differential potentiometric titration technique is described which allows the determination of dissociation constants of sparingly soluble and/or labile compounds. The dissociation constants of a series of beta-blockers were determined by this technique. Dissociation constants determined by routine potentiometric titration techniques were found to be equivalent to those determined by the differential potentiometric titration method

By using a computer to accumulate the titration data, it is shown that the dissociation constants of compounds which degrade due to added titrant base can be accurately determined. This is accomplished by shortening the duration of the experiment (total time < 10 minutes) such that minimal degradation occurs during the course of the titration. By combining the computer technique with a differential potentiometric titration technique, it is possible to determine the dissociation constants of sparingly soluble compounds which are not stable in solution

In the determination of dissociation constants, if two pKs are separated by less than 4 pH units, then these constants are said to overlap. To accurately determine a pK, both dissociation constants must be solved for simultaneously. A method is described which corrects for overlapping pKs in a differential potentiometric titration, which then allows the unambiguous determination of the dissociation constants. Also described is a method to correct the differential titration when the amount of overlap is small and the pK of one of the overlapping constants is known