摘要
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 ,2 5℃下其水合反应的表观速率常数kobs=7 76× 10 - 6 ·min- 1 ,半衰期t1 2 =6 2d ;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kobs=(2 6 1+2 1 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 =(k1 k2 ) [l OHP] k- 1 ,加入H+ 则速率方程为r=(k1 +K0 k3[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 。
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 76×10 -6 ·min -1 and the half life t 1/2 was 62 days at 25 ℃ . In the presence of H +, the aquation could be accelerated by H +according to the equation k obs =(2 61+21 9[H +])×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 =( k 1 k 2)[ l OHP]/ k -1 in the absence of H + and r =( k 1+ K 0 k 3[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.
出处
《药学学报》
CAS
CSCD
北大核心
2003年第3期223-226,共4页
Acta Pharmaceutica Sinica
关键词
奥沙利铂
水合反应
一级反应
反应机理
oxaliplatin
aquation
the first order reaction
reaction mechanism
