常山碱稳定性及其降解动力学研究(1)
[摘要]對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 90)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8333%，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 14)还是人工肠液(pH 68)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027%，76%，539%。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。
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[关键词]常山碱；稳定性；高效液相色谱法
Investigation on stability and degradation kinetics of febrifugine
ZHANG Jiyuan1，2，3， LIU Xiaoqian2，3， YANG Lixin2，3， FENG Weihong2，3， WANG Zhimin2，3*， LI Chun2，3
(1. School of Traditional Chinese Medicine， Capital Medical University， Beijing 100069， China；
2. China Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China；
, 百拇医药
3. National Engineering Laboratory for Quality Control Technology of Chinese Herbal Medicines， Beijing 100700， China)
[Abstract]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 90) The higher the temperature， the worse the stability of febrifugine At 4080 ℃， the content of febrifugine was decreased to be 60% of its initial content in 10 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 8333% 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 14) and artificial intestinal fluid (pH 68)， 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 027%， 76% and 539%， respectively The degradation of febrifugine basically complied with the firstorder 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 purification of febrifugine or the production of the related preparations， it should be done fast in the acidic solution， low temperature and dark conditions， while the febrifugine solid should be kept in dry and dark conditions, 百拇医药(张继远刘晓谦杨立新冯伟红 王智民 李春)
, http://www.100md.com
[关键词]常山碱；稳定性；高效液相色谱法
Investigation on stability and degradation kinetics of febrifugine
ZHANG Jiyuan1，2，3， LIU Xiaoqian2，3， YANG Lixin2，3， FENG Weihong2，3， WANG Zhimin2，3*， LI Chun2，3
(1. School of Traditional Chinese Medicine， Capital Medical University， Beijing 100069， China；
2. China Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China；
, 百拇医药
3. National Engineering Laboratory for Quality Control Technology of Chinese Herbal Medicines， Beijing 100700， China)
[Abstract]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 90) The higher the temperature， the worse the stability of febrifugine At 4080 ℃， the content of febrifugine was decreased to be 60% of its initial content in 10 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 8333% 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 14) and artificial intestinal fluid (pH 68)， 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 027%， 76% and 539%， respectively The degradation of febrifugine basically complied with the firstorder 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 purification of febrifugine or the production of the related preparations， it should be done fast in the acidic solution， low temperature and dark conditions， while the febrifugine solid should be kept in dry and dark conditions, 百拇医药(张继远刘晓谦杨立新冯伟红 王智民 李春)