Determination of dissociation constants of polyprotic acids from chromatographic data

The separation and purification of drugs and biological compounds, which are typically weak polyprotic acids, by HPLC is the subject of numerous literature reports. The development of separation methodologies depends on the acid dissociation constants, and the HPLC offers a valuable method for determining these constants, especially when the compounds are poorly soluble in water. This review presents general basic equations and shows how they are used for determining the pKa's. It also discusses the parameters affecting the pKa's and the methods of their measurement as presented in a representative number of research papers published in the last 20 years.