摘要
目的:研究益母草碱(leonurine,LE)在不同溶液中的稳定性,探讨其降解动力学特性。方法:通过经典恒温试验,采用HPLC法测定LE在不同pH溶液(pH范围2.0～11.0)及常用有机溶剂(甲醇、乙醇、异丙醇、乙腈)中的浓度,计算降解动力学参数。富集主要降解产物,利用核磁共振进行结构鉴定,推断其降解过程。结果:LE在酸性及中性溶液中较稳定,在碱性水溶液(pH=11.0)与甲醇中,遇热稳定性发生明显变化,降解反应速率常数k分别为1.700 4和1.395μg·m L^(-1)·h^(-1),t0.9分别为1.94与3.38 h,均呈现零级动力学降解特征,主要降解产物分别为丁香酸与丁香酸甲酯。结论:LE在碱性溶液与甲醇中遇热不稳定,在制剂的制备过程中应注意温度和溶剂的选择。该研究为益母草碱制剂的开发提供了理论指导和数据支持。
Objective： To investigate the stability and degradation kinetic characteristics of leonurine（ LE）in different solutions. Methods： The classical isothermal method was employed to evaluate the degradation kinetic profile of LE in different pH solution and commonly used organic solvent（ methanol,ethanol,isopropanol,and acetonitrile）. The concentration of LE was determined by HPLC method. The degradation kinetic parameters were calculated. Moreover,the structures of main degradation products were identified by1 H nuclear magnetic resonance（1 H NMR） and the degradation process was concluded. Results： LE was stable both in acidic and neutral solutions. The thermal degradation kinetic of LE in alkaline aqueous solution（ pH = 11. 0） and methanol followed zero-order process. The degradation rate constant k of LE were 1. 700 4 and 1. 395 μg·m L-1·h-1,while t0. 9 were1. 94 and 3. 38 h in aqueous solution（ pH 11. 0） and methanol,respectively. Both behave zero-order kinetic degradation characteristics. The main degradation products were syringic acid and methyl syringate. Conclusion：LE was labile in alkaline solution and methanol. So temperature and solvent should be noticed during the preparation process. Our data provided a theoretical guidance in the future pharmaceutical utilization research of LE.
作者
周云琍
尹丽娜
张雅雯
赵鹏飞
陈晓晓
郑高利
梁泽华
王胜浩
ZHOU Yun-li;YIN Li-na;ZHANG Ya-wen;ZHAO Peng-fei;CHEN Xiao-xiao;ZHENG Gao-li;LIANG Ze-hua;WANG Sheng-hao(Zhejiang Chinese Medical University,Hangzhou 310051,China;Zhejiang Academy of Medical Sciences,Hangzhou 310012.China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第19期2297-2301,共5页
Chinese Journal of New Drugs
基金
浙江省医药卫生科技计划项目(2018KY349)
浙江省基础公益研究计划(LQY18H300002)
关键词
益母草碱
降解动力学
稳定性
经典恒温试验
结构
leonurine
degradation kinetics
stability
classical constant temperature experiment
structure
