利考苯达唑在水溶液中的稳定性。

Stability of ricobendazole in aqueous solutions.

作者信息

Wu Zimei, Tucker Ian G, Razzak Majid, Medlicott Natalie J

机构信息

School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.

出版信息

J Pharm Biomed Anal. 2009 Jul 12;49(5):1282-6. doi: 10.1016/j.jpba.2009.02.032. Epub 2009 Mar 13.

DOI:10.1016/j.jpba.2009.02.032

PMID:19342190

Abstract

The chemical stability of ricobendazole (RBZ) was investigated using a stability-indicating high performance liquid chromatographic (HPLC) assay with ultraviolet detection. The degradation kinetics of RBZ in aqueous solution was evaluated as a function of pH, buffer strength and temperature. The oxidation reaction in hydrogen peroxide solution was also studied. Degradation products were analyzed by mass spectroscopy and degradation pathways are proposed. Degradation of RBZ followed pseudo first-order kinetics and Arrhenius behavior over the temperature range 24-55 degrees C. A V-shaped pH-rate profile over the pH range 2-12 was observed with maximum stability at pH 4.8. The shape of the pH-rate profile was rationalized by catalytic effects of various components in the solution on each RBZ species. At pH 11 the activation energy for hydrolysis was 79.5 kJ/mol, and phosphate catalysis was not observed. Oxidation occurred in hydrogen peroxide solutions and was catalyzed by the presence of copper (Cu(2+)) ions. Ricobendazole amine and albendazole sulfone were identified by MS assay to be the degradation products of hydrolysis and oxidation respectively.

摘要

采用具有紫外检测功能的稳定性指示高效液相色谱（HPLC）法研究了瑞考苯达唑（RBZ）的化学稳定性。评估了RBZ在水溶液中的降解动力学与pH值、缓冲强度和温度的关系。还研究了RBZ在过氧化氢溶液中的氧化反应。通过质谱分析降解产物并提出降解途径。在24 - 55℃温度范围内，RBZ的降解遵循准一级动力学和阿伦尼乌斯行为。在pH值2 - 12范围内观察到V形pH - 速率曲线，在pH 4.8时稳定性最高。通过溶液中各组分对每种RBZ物种的催化作用解释了pH - 速率曲线的形状。在pH 11时，水解的活化能为79.5 kJ/mol，未观察到磷酸盐催化作用。在过氧化氢溶液中发生氧化反应，且由铜（Cu(2+)）离子的存在催化。通过质谱分析确定瑞考苯达唑胺和阿苯达唑砜分别为水解和氧化的降解产物。