Determination of pka value of ambrisentan pharmaceutical active ingredient by HPLC method

Nowadays, determining the ionization behavior of pharmaceutical active substances is of great importance in terms of bioavailability, pharmacokinetics and formulation development studies. Especially the ionization constant (pKa) values of weakly acidic and basic drug compounds are among the critical parameters that directly affect the solubility, stability and permeation capacity of the drug through biological membranes. In this thesis, Ambrisentan, which is in the endothelin receptor antagonist group, is one of the compounds whose ionization behavior should be examined in detail due to being a lipophilic drug used in cardiovascular diseases. In this study, reverse phase high performance liquid chromatography (RP-HPLC) method was applied to determine the pKa value of Ambrisentan compound; pKa determinations were carried out at different acetonitrile-water ratios in order to examine the solubility and ionization behavior depending on the changes in the solvent system. The obtained data were evaluated based on the 1/Ɛ–pKa and XACN–pKa relationships and the pKa values of Ambrisentan in water media were determined. It is believed that the data obtained from this study and the developed method will contribute to the literature by demonstrating potential use in pharmaceutical analyses. Keywords: Ambrisentan, pKa, HPLC.