The partition behaviors of amphoteric acids with pH were examined based on the theoretical considerations. The apparent partition coefficient, defined as the ratio of the activities of the acid in organic and aqueous phases, is maximal at the isoelectric point. When pK₁, is much smaller than pK₂, the apparent partition coefficient coincides with the true partition coefficient, defined as the ratio of the activities of the neutralform of the acid in the two phases, at this point. The former changes linearly with slopesof +1 and-1 in the region of pK₁>>pH and pK₂<<pH. By applying the method of Ang when the presence of the zwitter-ionic form can be excluded, it was demonstrated that the true partition coefficient can be determined exactly from this pH-partition curve, even if the ionization constants of the acid are not known. This method also gives the values of the two ionization constants, so it seemed to be available for determination of the ionization constants of acids, which are very slightly soluble in water.
The partition coefficients of p-aminobenzoic acid, sulfonamide and sulfamonomethoxine were measured in an n-octanol/H₂O system at 25°over a wide pH range. The variation of the partition coefficients with pH confirmed the above considerations well. The values obtained for the true partition coefficients and ionization constants agreed well with the results of others.