Determination of pK Values for Some Tyrosine Kinase Inhibitors Using the Reversed-Phase Liquid Chromatography

The drug dissociation constant (pK) describes the ionization/protonation states. This physicochemical feature has a direct effect on the ADME properties of the active pharmacological compounds. In this study, using the LC method, the dependence of retention of tyrosine kinase inhibitors, erlotinib, canertinib, and bosutinib which are used in targeted therapy for several types of cancer, on the mobile phase pH was investigated at three different acetonitrile–water buffer compositions, and experimental data were utilized to calculate pK values and capacity factors. Afterward, Yasuda–Shedlovsky extrapolation and mole fraction of acetonitrile plot used in order to acquire the pK in aqueous medium. The observed results have been carefully compared to those reported in the literature that were obtained by different approaches. The conclusion is that these findings emphasize the potential of the physicochemical features of medications to aid in the comprehension of several biological systems, including human oral absorption, cell permeability, and protein binding in plasma. In addition, the pK values of these ionizable molecules in various water–organic binary solutions are useful for the development of separation techniques focused on reversed-phase liquid chromatography and capillary electrophoresis.