Kinetic and thermodynamic analysis of 10-hydroxy-camptothecin hydrolysis at physiological pH

To derive accurately the thermodynamic parameters governing the hydrolysis of the lactone ring at physiological pH, a derivative spectrophotometric technique was used for the simultaneous estimation of lactone and carboxylate forms of the 10-hydroxy-camptothecin (10-HC). Validation of the analytical method was done with respect to reproducibility, percent recovery, and level of detection. Hydrolysis of the lactone ring of 10-HC followed a 1st order decay with a rate constant equal to (0.0281 ± 0.001) min−1 in PBS at pH 7.4 and at a temperature of 310 K. The activation energy for the hydrolysis reaction as calculated from the Arrhenius equation was (79.41 ± 0.92) kJ · mol−1, whereas the enthalpy and entropy of hydrolysis of 10-hydroxy-camptothecin were on average 12.45 kJ · mol−1 and 52.37 J · K−1 · mol−1, respectively. The positive enthalpy and entropy values of the 10-HC-lactone hydrolysis indicate that the reaction is endothermic and entropically driven.