摘要
目的以金银花口服液为研究对象,通过抗炎质量标志物的辨识和筛选,建立工艺全过程的质量溯源评价方法。方法采用UPLC/Q-TOF-MS对口服液中的环烯醚萜和酚酸类成分进行解析,通过分子网络技术构建关联关系;采用HPLC法建立多批次口服液的指纹图谱,进行相似度分析辨识关键药效分子;通过NF-κB双荧光报告系统确证关键抗炎质量标志物;进一步基于双波长HPLC技术分别建立口服液中环烯醚萜和酚酸类12种质量标志物的定量方法。通过对原料药材、制剂加工过程中质量标志物提取转移率以及热稳定性等的考察,实现对口服液的质量评价。结果口服液中共鉴定出9种环烯醚萜和6种酚酸类成分,描绘了成分之间可能存在的转换关系。11批次口服液的指纹图谱分析结果显示主要色谱峰组成基本一致,相似度大于90%,其中6种环烯醚萜(马钱苷酸、断氧化马钱苷酸、断马钱子酸、当药苷、断氧化马钱子苷、断马钱子苷)和6种酚酸成分(新绿原酸、绿原酸、隐绿原酸、异绿原酸B、异绿原酸A、异绿原酸C)为具有NF-κB抑制活性的主要药效成分,可作为质量标志物。利用双波长HPLC法在多批次的生产过程中对上述12种质量标志物的溯源传递进行了考察发现口服液的制备工艺稳定,总环烯醚萜和总酚酸的含量基本保持稳定,但成分之间部分会发生转化。在提取、浓缩以及制剂工艺过程中,环烯醚萜和酚酸类成分的转移率分别超过了76%和63%。结论本文所建方法稳定可靠、操作简便,可以对金银花口服液工艺全过程进行高效的质量溯源评价,为药材和制剂的全程质量监管提供了有效手段。
Objective To establish a quality traceability evaluation method for the whole honeysuckle oral solution process by identifying and screening its anti-inflammatory quality markers.Methods UPLC/-TOF-MS was used to analyze the iridoids and phenolic acids in oral solution,and the correlations were constructed by molecular network technology.The HPLC fingerprints of multiple batches of oral solution were established,and similarity analyses were performed to identify key pharmacodynamic molecules.The key anti-inflammatory quality markers were confirmed by the NF-κB dual luciferase assay system.Further,the quantification of 12 quality markers of iridoids and phenolic acids in oral solution was established separately based on the dual-wavelength HPLC technique.The quality of the oral solution was evaluated by examining the extraction and transfer rate of quality markers during the processing of raw materials and preparations and thermal stability.Results A total of 9 iridoids and 6 phenolic acids were identified in the oral solution,and the possible conversion relationships between their components were depicted.Fingerprint analysis of 11 batches of oral liquids showed that the composition of their main peaks was the same,with a similarity of more than 90%.Among them,6 iridoids(loganic acid,secologanoside,secologanic acid,sweroside,secoxyloganin,secologanin)and 6 phenolic acids(neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,isochlorogenic B,isochlorogenic A,isochlorogenic C)exhibited NF-κB inhibitory activity,which were the main pharmacological components and could be used as quality markers.The traceability of the above 12 quality markers was investigated in a multi-batch process based on the dual-wavelength HPLC method.The thermal stability studies of the raw materials revealed that the contents of their total iridoids and phenolic acids remained stable.Still,some of them would be transformed between components.The production process of the oral solution was stable,and the transfer rates of the iridoids and phenolic acids during the extraction,concentration and preparation were over 76%and 63%,respectively.Conclusion The method is stable,reliable,easy to operate and can evaluate the full honeysuckle oral solution process,which provides an effective means for the quality control of honeysuckle herbs and preparations.
作者
刘凯昕
程传景
田璐
崔晶
王鹤辰
侯媛媛
白钢
Liu Kaixin;Cheng Chuanjing;Tian Lu;Cui Jing;Wang Hechen;Hou Yuanyuan;Bai Gang(State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy,Nankai University,Tianjin 300353,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第11期3469-3477,共9页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会面上项目(81973449):基于氧化呼吸链的中医清热的化学物质基础及其生物学机制研究,负责人:侯媛媛
关键词
金银花口服液
环烯醚萜
酚酸
质量标志物
溯源传递
Honeysuckle oral liquid
Iridoid
Phenolic acid
Quality markers
Traceability and transmission
