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目的研究奥沙利铂溶液在不同温度、pH条件下水解动力学,以及缓冲盐对药物水解的影响。方法采用高效液相色谱法测定奥沙利铂的水解产物草酸和杂质B含量,进一步推导出奥沙利铂水解过程,并运用经典恒温法探讨其稳定性。结果奥沙利铂水溶液在不同温度、pH条件下的水解反应均符合一级动力学,水解活化能为60.9 kJ.mol-1,且在pH 4.2时最稳定。此外缓冲盐会加速药物的水解作用,缓冲盐浓度与药物水解程度呈正相关。结论奥沙利铂在水溶液中易水解,故在药物的溶解和新制剂研究的过程中都应当严格控制工艺条件。
Objective To study the kinetics of oxaliplatin hydrolysis under different temperature and pH conditions and the effects of buffer salts on drug hydrolysis. Methods The contents of oxalic acid and impurity B in oxaliplatin were determined by high performance liquid chromatography (HPLC). The hydrolysis of oxaliplatin was further deduced. The stability of oxaliplatin was also investigated by classical thermostat method. Results The hydrolysis of oxaliplatin aqueous solution under different temperature and pH conditions was in accordance with the first order kinetics. The hydrolytic activation energy was 60.9 kJ · mol-1 and was the most stable at pH 4.2. In addition buffer salt will accelerate the hydrolysis of drugs, buffer salt concentration and the degree of drug hydrolysis was positively correlated. Conclusion Oxaliplatin is easily hydrolyzed in aqueous solution, so the process conditions should be strictly controlled in the process of drug dissolution and new formulation research.