基于质量源于设计理念多指标综合优选护肝解酒合剂提取工艺

Multi-index integrated evaluation optimizes extraction process of Hugan Jiejiu Mixture based on quality by design(QbD)concept

目的:基于质量源于设计理念,采用多指标综合评分法优选护肝解酒合剂的提取工艺,提高工艺过程的质量控制水平。方法:以3'-羟基葛根素、栀子苷、葛根素、3'-甲氧基葛根素、葛根素芹菜糖苷、二氢杨梅素、橙皮苷和人参皂苷Rb1为关键质量属性(critical quality attributes,CQAs),采用HPLC法建立了同时测定3'-羟基葛根素、栀子苷、葛根素、3'-甲氧基葛根素、葛根素芹菜糖苷、二氢杨梅素和橙皮苷含量的方法和人参皂苷Rb1的含量测定方法。以CQAs的主成分综合评分为考察指标,采用正交试验设计法优选最佳提取工艺参数。结果:3'-羟基葛根素、栀子苷、葛根素、3'-甲氧基葛根素、葛根素芹菜糖苷、二氢杨梅素、橙皮苷和人参皂苷Rb1在一定质量浓度范围内线性关系良好(r≥0.9991),平均加样回收率在95.2%~102.8%,RSD≤3%。最佳提取工艺为药材加10倍量水、提取2次、每次1 h。结论:建立的多成分含量测定方法简单准确,优选出的提取工艺稳定可行,可为护肝解酒合剂临床应用和新药开发提供参考。

OBJECTIVE To optimize the extraction process of Hugan Jiejiu Mixture by multi-index comprehensive scoring based on quality by design(QbD)concept,so as to improve the quality control level in the extraction process.METHODS The compounds of 3'-hydroxy puerarin,geniposide,puerarin,3'-methoxy puerarin,puerarin apioside,dihydromyricetin,hesperidin and ginsenoside Rb1 were chosen as critical quality attributes(CQAs).HPLC was used to simultaneously determine contents of 3'-hydroxy puerarin,geniposide,puerarin,3'-methoxy puerarin,puerarin apioside,dihydromyricetin and hesperidin.The determination of ginsenoside Rb1was performed by HPLC.Orthogonal test Design was used to optimize the extraction process parameters,with the principal component analysis scores of CQAs chosen as integrated evaluation scores of synthesis indexes.RESULTS 3'-Hydroxy puerarin,geniposide,puerarin,3'-methoxy puerarin,puerarin apioside,dihydromyricetin,hesperidin and ginsenoside Rb1 had good linear relationship within a certain mass concentration range(r≥0.9991).The average recovery rates were in range of 95.2%-102.8%,with RSD≤3%.The optimal extraction process was as follows:the prescription drugs were extracted for twice,each time for 1 h,with 10 times water.CONCLUSION The multiple compounds determination method is simple and accurate.The optimized extraction process is stable and feasible,and can provide reference for further clinical application and new drug development.