Method of UV-Metric and pH-Metric Determination of Dissociation Constants of Ionizable Drugs: Valsartan

  • Milan MelounEmail author
  • Lucie Pilařová
  • Aneta Pfeiferová
  • Tomáš Pekárek


Valsartan is used for treating high blood pressure, congestive heart failure and to increase the chances of living longer after a heart attack and to reduce the mortality rate for people with left ventricular dysfunction following a heart attack. Regression analysis of the pH-spectra with REACTLAB and of the pH-titration curve with ESAB determined two close consecutive dissociation constants. MARVIN and ACD/Percepta predicted two protonation sites. In water a soluble anion L2− forms two sparingly soluble species LH, LH2. Although adjusted pH less affected the spectral changes in the chromophore, \({\text{p}}K_{a1}^{\text{T}}\) = 3.70 ± 0.12, \({\text{p}}K_{a2}^{\text{T}}\) = 4.82 ± 0.08 at 25 °C and \({\text{p}}K_{a1}^{\text{T}}\) = 3.44 ± 0.08, \({\text{p}}K_{a2}^{\text{T}}\) = 4.67 ± 0.02 at 37 °C in an aqueous phosphate buffer were determined. By regression analysis of potentiometric pH-titration curves and \({\text{p}}K_{a1}^{\text{T}}\) = 3.51 ± 0.01, \({\text{p}}K_{a2}^{\text{T}}\) = 4.63 ± 0.01, at 25 °C and \({\text{p}}K_{a1}^{\text{T}}\) = 3.44 ± 0.03, \({\text{p}}K_{a2}^{\text{T}}\) = 4.51 ± 0.03 at 37 °C in an aqueous medium were estimated. Positive enthalpy values ΔH0(pKa1) = 10.33 kJ·mol−1, ΔH0(pKa2) = 17.70 kJ·mol−1 showed that the dissociation process was endothermic. The standard state Gibbs energy changes are ΔG0(pKa1) = 20.03 kJ·mol−1, ΔG0(pKa2) = 26.43 kJ·mol−1 at 25 °C and the ΔS0 at 25 °C and 37 °C are (ΔS0(pKa1) = − 32.56 J·K−1·mol−1, ΔS0(pKa2) = − 29.26 J·K−1·mol−1 at 25 °C and ΔS0(pKa1) = − 30.01 J·K−1·mol−1, ΔS0(pKa2) = − 25.92 J·K−1·mol−1 at 37 °C.

Graphic Abstract


Dissociation constants Valsartan Spectrophotometric titration pH-titration REACTLAB SQUAD84 ESAB 


Supplementary material

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Authors and Affiliations

  1. 1.Department of Analytical ChemistryUniversity of PardubicePardubiceCzech Republic
  2. 2.Zentiva k.sPragueCzech Republic

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