奥沙利铂的水合反应及其酸度的影响

目的研究不同温度时奥沙利铂的水合反应以及酸度的影响,获到相关的动力学数据,为临床用药提供指导。方法用电导法和高效液相色谱法测定反应体系中反应物随时间变化情况。结果奥沙利铂的水合反应遵循一级反应的规律,在水溶液介质中不加H⁺时,25 ℃下其水合反应的表观速率常数k_obs=7.76×10^-6·min^-1,半衰期t_1/2=62 d;当加入H⁺时,水合反应的表观速率常数随H⁺浓度的增加而增大,且有k_obs=(2.61+21.9［H⁺］)×10^-4·min^-1。提出了水合反应机理,并由此推导出不加H⁺时奥沙利铂水合反应速率方程为r=(k₁k₂)［L-OHP］/k-1,加入H⁺则速率方程为r=(k₁+k0k₃［H⁺］)［L-OHP］,与试验结果相吻合。结论奥沙利铂的水溶液比较稳定,符合临床用药的要求。

The aquation of oxaliplatin and the effect of acid

AIM: To investigate the aquation of oxaliplatin in aqueous solution at different temperatures and gain the kinetic data. METHODS: Electronic conductometry and high performance liquid chromatography (HPLC) were used to measure the oxaliplatin content in the reaction systems at different time. RESULTS: The aquation of oxaliplatin followed a pseudo-first-order rate law. In the absence of H+, the observed rate constant kobs was 7.76 x 10(-6).min-1 and the half life t1/2 was 62 days at 25 degrees C. In the presence of H+, the aquation could be accelerated by H+ according to the equation kobs = (2.61 + 21.9 H+]) x 10(-4).min-1. The mechanism of aquation has also been proposed in this paper. From the mechanism, the rate of aquation following to r = (k1 k2) l-OHP]/k-1 in the absence of H+ and r = (k1 + K0k3 H+]) l-OHP] in the presence of H+ have been deduced, which were in perfect agreement with the experimental results. CONCLUSION: In the absence of H+, the aqueous solution of oxaliplatin is stable, which meets to the request of clinical.