Multiwavelength UV-metric and pH-metric determination of the multiple dissociation constants of the lesinurad

Publication date: 5 September 2018Source: Journal of Pharmaceutical and Biomedical Analysis, Volume 158Author(s): Milan Meloun, Aneta Čápová, Lucie Pilařová, Tomáš PekárekAbstractPotentiometric and spectrophotometric pH-titrations of the lesinurad for three consecutive dissociation constants determination were compared. Lesinurad is a selective inhibitor of uric acid reabsorption as part of a combination of medicines to treat high levels of uric acid in blood, also called hyperuricemia. Nonlinear regression of the pH-spectra with REACTLAB and SQUAD84 and of the pH-titration curve with ESAB determined three multiple close dissociation constants. The protonation scheme of lesinurad was suggested. A sparingly soluble anion L− of lesinurad was protonated to the still soluble species LH, LH2+ and LH32+ in pure water. Three consecutive thermodynamic dissociation constants were estimated pKTa1 = 2.09, pKTa2 = 4.25, pKTa3 = 6.58 at 25 °C and pKTa1 = 1.96, pKTa2 = 4.16, pKTa3 = 6.32 at 37 °C by UV-metric spectra analysis. The graph of molar absorption coefficients shows that the spectrum of species LH2+ and LH vary in colour, while protonation of chromophore LH2+ to LH32+ has less influence on chromophores in the lesinurad molecule. Three multiple thermodynamic dissociation constants of 1 × 10−4 M lesinurad were determined by the pH-metric analysis pKTa1 = 2.39, pKTa2 = 3.47, pKTa3 = 6.17 at 25 °C and pKTa1 = 2.08, pK...

Source: Journal of Pharmaceutical and Biomedical Analysis - July 10, 2018 Category: Drugs & Pharmacology Source Type: research