Kinetic studies of the hydrolysis and lactonization of camptothecin and its derivatives, CPT-11 and SN-38, in aqueous solution

Article abstract of DOI:10.1248/cpb.42.2135

The effect of pH and temperature on the reaction rate of the hydrolysis and lactonization of camptothecin and its derivatives, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and 7-ethyl-10-hydroxycamptothecin (SN-38), in aqueous solution was studied by high-performance liquid chromatography or two-wavelength spectrophotometry. Hydrolysis and lactonization of each compound progressed according to pH- and temperature-dependent pseudo-first-order kinetics. The ratio of the lactone form of each compound to its hydroxy-acid form was determined mainly by the pH of the solution and was not influenced by temperature. Half-lives of the lactone and hydroxy-acid forms of CPT-11 at 37°C and pH 7.4 were 13.7 min and 4.25 h, respectively.