Determination of the thermodynamic dissociation constant of capecitabine using spectrophotometric and potentiometric titration data

Capecitabine has been studied by a combined potentiometric and spectrophotometric titration at T = (298.15, 310.15) K at different ionic strengths. The thermodynamic dissociation constant was estimated by non-linear regression of {pKa, I} data: pKaT=8.97(1) at T = 298.15 K and pKaT=8.74(0) at T = 310.15 K, where the figure in the brackets is the standard deviation in last significant digits. Thermodynamic parameters ΔH°/kJ · mol−1 and ΔS°/J · K−1 · mol−1 have been determined from the temperature variation of thermodynamic dissociation constants. The value of enthalpy ΔH° = 33.9 kJ · mol−1 shows the dissociation process is endothermic and the value of entropy ΔS° = −51.9 J · K−1 · mol−1 indicates that the dissociation is not a spontaneous process.

Research highlights► Capecitabine is a novel oral tumor-activated and chemotherapeutic agent . ► The thermodynamic dissociation constant 8.97(1) at 298.15 K and 8.74(0) at 310.15 K. ► Enthalpy ΔH° = 33.9 kJ · mol−1 shows the dissociation process is endothermic. ► Entropy ΔS° = −51.9 J · mol−1 indicates not-spontaneous process.