依替巴肽注射液质量评价研究  

Quality Evaluation of Eptifibatide Injection

作　　者：秦玉盈 杨洪淼 邓利娟 韩苗苗 刘万卉[1] 范慧红 QIN Yuying;YANG Hongmiao;DENG Lijuan;HAN Miaomiao;LIU Wanhui;FAN Huihong(School of Pharmacy,Yantai University,Yantai 264003,China;NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Institute for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]烟台大学药学院,山东烟台264003 [2]中国食品药品检定研究院化学药品检定所,国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国药学杂志》2023年第24期2267-2273,共7页Chinese Pharmaceutical Journal

摘　　要：目的评价国内依替巴肽注射液的质量现状及存在问题,为药品安全监管和质量标准完善提供参考。方法对国家抽检的样品进行法定检验,针对现行企业注册标准参差、个别有关物质测定方法不合理,缺少聚合物的控制,缺少活性研究数据、企业对照品赋值的准确性等问题,开展了多个项目的探索性研究工作。结果3家生产企业的16批样品法定检验合格率100%。探索性研究完善了有关物质分析方法并对有关物质进行重新评价,均符合拟定限度规定;建立依替巴肽聚合物测定方法及液相色谱-质谱(LC-MS)鉴别方法,测定结果发现部分样品中依替巴肽三聚体和四聚体的含量偏高;建立依替巴肽体外活性测定方法,研究结果加深了对该药物作用机制的认识;企业对照品的赋值存在不准确的问题。结论国产依替巴肽注射液虽然全部合格,但不同企业的产品质量仍有差距,建议尽快统一和完善国家标准并建立依替巴肽国家对照品,以提高产品质量,更好地保证患者安全用药。OBJECTIVE To evaluate the quality status and existing problems of eptifibatide injection,and provide reference for drug safety supervision and standards improvement.METHODS The samples from national sampling evaluation were tested by statutory standards.Exploratory research work was carried out basing on the found problems,such as significant differences between the current registration standards,some test methods of related substances being unreasonable,lack of polymer control,lack of data for activity research,and inadequate accuracy of enterprise reference material assignment.RESULTS The pass rate through statutory testing of 16 batches of samples from three manufacturers was 100%.The exploratory research improved the test method of related substances,all of the samples were qualified with the proposed limits;the determination method and LC-MS identification method for eptifibatide polymer were established,the results showed that the contents of eptifibatide trimer and tetramer in some samples were relatively high;the establishment of an in vitro activity assay method for eptifibatide has deepened our understanding of the mechanism of the drug;the assignment of enterprise reference materials was inaccurate.CONCLUSION Although all of the eptifibatide injections are qualified,the quality of products from different manufacturers are not the same.It is recommended to unify and improve national standards and establish national reference material of eptifibatide as soon as possible,so as to improve the quality of products and the safety on medication.

关 键 词：依替巴肽 质量标准 质量评价 合成肽 注射液 

分 类 号：R917[医药卫生—药物分析学]