常山碱稳定性及其降解动力学研究  

Investigation on stability and degradation kinetics of febrifugine

作　　者：张继远[1,2,3] 刘晓谦[2,3] 杨立新[2,3] 冯伟红[2,3] 王智民[2,3] 李春[2,3] 

机构地区：[1]首都医科大学中医药学院,北京100069 [2]中国中医科学院中药研究所,北京100700 [3]中药质量控制技术国家工程实验室,北京100700

出　　处：《中国中药杂志》2017年第16期3178-3184,共7页China Journal of Chinese Materia Medica

基　　金：国家"重大新药创制"科技重大专项(2014ZX09304307001-002-008;2015ZX09501004);国家科技支撑计划项目(2011BAI07B08)

摘　　要：对常山碱的稳定性及其降解动力学进行研究。结果表明,24 h内流动相作溶剂时,常山碱含量仅降低1%,但在水、甲醇、50%甲醇及10%乙腈溶液中其含量降低为起始含量的90%。当溶液pH介于3~7时,24 h内常山碱的保留率在98%以上,但在碱性溶液中(pH 9.0)含量降低约12%。温度越高,常山碱稳定性越差,40~80℃放置10 h后,常山碱降为起始含量的60%左右,但在20℃下放置10 h,其含量仅降低约5%;40,60℃放置10 h,常山碱主要转化为异常山碱,二者的总含量较起始总含量基本不变,但是80℃下放置10 h,常山碱和异常山碱的总含量降低为起始总含量的83.33%,说明高温下常山碱结构发生了彻底改变,而不仅仅是异构化为异常山碱。光照对常山碱稳定性影响显著,强光照射108 h,常山碱质量分数较起始含量降低23%左右,但在避光和自然光条件下,其含量仅降低10%左右。无论在人工胃液(pH 1.4)还是人工肠液(pH6.8)中,放置10 h后,常山碱质量分数降低均小于5%。常山碱固体在高温(60℃)、高湿[(75±1)%]和强光(3 000 lx)照射下放置10 d后,其含量分别减少0.27%,7.6%,5.39%。常山碱在水、甲醇、50%甲醇和10%乙腈溶剂中、碱性溶液、不同光照和不同温度(20,40℃)下的降解基本符合化学动力学一级反应。因此,无论是常山碱的制备纯化还是相关制剂的生产,都应在偏酸性溶液,低温、避光条件下快速操作完成,而常山碱固体则应在干燥、避光条件下保存。To investigate the stability and degradation kinetics of febrifugine. The results showed that within 24 hours,febrifugine content was decreased by only 1% in mobile phase solvent,but its content was decreased to be 90% of the initial content in the water,methanol,50% methanol and 10% acetonitrile solution. When the pH value of the solution was between 3 and 7,the retention rate of febrifugine in 24 hours was over 98%,but its content was decreased by about 12% in alkaline solution（ pH 9. 0）. The higher the temperature,the worse the stability of febrifugine. At 40-80 ℃,the content of febrifugine was decreased to be 60% of its initial content in10 hours,but the content was decreased by only 5% in 10 h at 20 ℃. However,no matter 40 ℃ or 60 ℃,febrifugine was mainly transformed into isofebrifugine,and the total content of febrifugine and isofebrifugine was equal to their initial total content in 10 hours,while incase of 80 ℃,the total content was decreased to be 83. 33% in 10 h,which suggested that the structure of febrifugine was absolutely changed,not just isomerized to be isofebrigugine at high temperature. Light had a significant impact on the stability of febrifugine. Under bright light,the content of febrifugine was reduced by about 23% in 108 h,but it only decreased by about 10% in the natural light or darkness. In artificial gastric fluid（ pH 1. 4） and artificial intestinal fluid（ pH 6. 8）,the content of febrifugine was decreased by less than 5% in 10 h. After storage at high temperature（ 60 ℃）,high humidity [（ 75 ± 1） %] and strong light（ 3 000 lx）conditions for 10 d,the content of solid febrifugine was decreased by 0. 27%,7. 6% and 5. 39%,respectively. The degradation of febrifugine basically complied with the first-order reaction kinetic process in the following conditions： in water,methanol,50% methanol and 10% acetonitrile solvents,alkaline solution（ pH 7）,different light intensity and different temperatures（ 20,40 ℃）. Therefore,no matter the isolation and p

关 键 词：常山碱 稳定性 高效液相色谱法 

分 类 号：R284.1[医药卫生—中药学]