摘要
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。
Abstract
OBJECTIVE To explore the hydrolysis kinetics of oxaliplatin solution under different pH and temperatures， and to evaluate the effect of buffer salts on its hydrolysis. METHODS The hydrolysates of oxaliplatin， oxalic acid， and impurity B were quantified by HPLC， then the hydrolysis process of oxaliplatin solution was deduced.While the stability of the solution was evaluated by classic isothermal method. RESULTS The hydrolysis reaction rate of oxaliplatin solution obeyed pseudo- first -order kinetics under different pH and temperatures， and the activating energy was 60.9 kJ·mol-1.It was most stable at pH 4.2. Besides， buffer salts could accelerate the hydrolysis. With the concentration of buffer salts increasing， the degree of hydrolysis increased. CONCLUSION Oxaliplatin was prone to hydrolysis， so the technological conditions should be under strict control during dissolution and the investigation of new- preparation.
关键词
奥沙利铂溶液 /
水解动力学 /
经典恒温法 /
高效液相色谱法
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Key words
oxaliplatin solution /
hydrolysis kinetics /
classic isothermal method /
high performance liquid chromatography (HPLC
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郑仁娟 张文成 梅兴国 龚伟 庞柯.
奥沙利铂水解动力学初步研究[J]. 中国药学杂志, 2011, 46(10): 781-784
ZHENG Ren-jun;ZHNG Wen-cheng;MEI Xing-guo;GONG Wei;PNG Ke.
Preliminary Study on Hydrolysis Kinetics of Oxaliplatin[J]. Chinese Pharmaceutical Journal, 2011, 46(10): 781-784
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参考文献
[1] MATH G， KIDANI Y， SEGIGUCHI M， et al. Oxalato-platinum or L-OHP， a third- generation platinum complex： an experimental and clinical appraisable and preliminary comparison with cisplatinum and carboplatinum [J]. Biom Pharm， 1989， 43(4： 237- 250.
[2] SUZUKIS R， TAKIZAWA T， KUWATA Y， et al. Effective anti-tumor activity of oxaliplatin encapsulated in transferin PEG- lipsome[J]. Inter J Pharm， 2008， 346(1-2： 143-150.
[3] ABULILA A S， KIZUKI S， DOI Y， et al. Oxaliplatin encapsulated in PEG-coated cationic liposomes induces significant tumor growth suppression via a dual-targeting approach in a murine solid tumor model [J]. J Controlled Release， 2009， 137(1： 8-14.
[4] CUI F D. Pharmaceutics(药剂学 [M]. 6th ed. Beijing： People′s Medical Publishing House， 2008：292-305．
[5] GAO W G， PU S P， LIU W P， et al. The aquation of oxaliplatin and the effect of acid [J]. Acta Pharm Sin(药学学报， 2003， 38(3： 223-226.
[6] ANDERSON N H， BLUNDELL R， BROWN S， et al. OXALIPLATIN FORMULATIONS： U S， 6306902B1 [P]. 2001-10-23.
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脚注
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