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Potentiometric 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 1×10−4M lesinurad were determined by the pH-metric analysis pKTa1=2.39, pKTa2=3.47, pKTa3=6.17 at 25°C and pKTa1=2.08, pKTa2=3.29, pKTa3=6.03 at 37°C. The values of enthalpy ΔH0(pKa1)=19.19kJmol−1, ΔH0(pKa2)=13.29kJmol−1, ΔH0(pKa3)=38.39kJmol−1, show the dissociation process is endothermic. The positive values of ΔG0(pKa1)=11.93kJmol−1, ΔG0(pKa2)=24.26kJmol−1, ΔG0(pKa3)=37.56kJmol−1 at 25°C indicate that the dissociation process of pKa2 is not spontaneous, which was confirmed by its value of entropy ΔS0(pKa1)=24.37Jmol−1, ΔS0(pKa2)=−36.79Jmol−1, ΔS0(pKa3)=2.79Jmol−1. Three macro-dissociation constants of lesinurad and protonation locations were predicted by MARVIN and ACD/Percepta.Lesinurad is the urate transporter inhibitor for treating hyperuricemia, which is associated with gout.Protonation equilibria were studied with UV-metric spectra analysis and pH-metric titration analysis.Three close pKTa1, pKTa2, pKTa3, of lesinurad were determined at 25°C and 37°C in an aqueous medium.The number of variously protonated species was estimated from the rank of the UV-absorbance matrix.Three multiple pKs and protonation locations were predicted by MARVIN and ACD/Percepta.Enthalpy and entropy prove the dissociation of lesinurad is exothermic and not spontaneous.