首批贝那鲁肽国家标准品的研制  

Development of the first national reference standard of beinaglutide

作　　者：丁晓丽[1] 吕萍[1] 蔡永清 段徐华[3] 王绿音 陈莹 徐可铮 李晶[1] 张伟[1] 胡馨月 李懿 孙悦[1] 张慧[1] 梁成罡[1] DING Xiao-li;LÜPing;CAI Yong-qing;DUAN Xu-hua;WANG Lü-yin;CHEN Ying;XU Ke-zheng;LI Jing;ZHANG Wei;HU Xin-yue;LI Yi;SUN Yue;ZHANG Hui;LIANG Cheng-gang(National Institutes for Food and Drug Control,Division of Hormone,Beijing 102629,China;Shanghai Benemae Pharmaceutical Corporation,Shanghai 201321,China;Shanghai Institute for Food and Drug Control,Shanghai 201203,China)

机构地区：[1]中国食品药品检定研究院激素室卫生部生物技术产品检定方法及其标准化重点实验室,北京102629 [2]上海仁会生物制药股份有限公司,上海201321 [3]上海市食品药品检验所,上海201203

出　　处：《药物分析杂志》2022年第1期78-85,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家科技重大专项课题资助项目(2018ZX09101001-003-004)。

摘　　要：目的:建立首批贝那鲁肽国家标准品。方法:采用质谱法、N-末端氨基酸序列测定、氨基酸比值法以及质量肽图法进行结构确证;采用HPLC法测定纯度;采用质量平衡法对原料药A(大规格样品)进行含量赋值,然后以原料药A为对照品,采用HPLC外标法对原料药B(待标品)的含量进行标定;采用体外细胞培养法对原料药B(待标品)进行效价测定。并对原料药B(待标品)稳定性及均一性进行了考察。结果:确证了贝那鲁肽的结构,并确定了首批贝那鲁肽国家标准品的含量为0.932 mg·支^(-1),生物效价为1.0×10^(4)U·支^(-1)。原料药B(待标品)分别在4℃及25℃,RH 80%条件下放置10 d,纯度无明显下降,光照10 d纯度明显下降。15支原料药B(待标品)含量测定结果的RSD为0.86%,均一性良好。结论:首批贝那鲁肽国家标准品可作为贝那鲁肽及相关制剂HPLC法鉴别、含量测定及生物活性测定用标准品。Objective:To establish the first national reference standard of beinaglutide.Methods:TOF-MS,N-terminal sequence determination,ratio coefficient of amino acid,peptide mapping were used to confirm the structure of beinaglutide.The purity was determined by HPLC.The content of active pharmaceutical ingredients A(API,sample of large size)was determined by mass balance method.Using API A as reference substance,the content of API B(candidate standard)was determined by HPLC external standard method.The potency of API Bwas determined by cell culture in vitro.Andthe stability and uniformity of API B(the candidate preparation)were investigated.Results:The structure of the beinaglutide was confirmed,the content of the first beinaglutide natio-nal reference standard was assigned as 0.932 mg per ampoule and the potency was 1.0×10^(4)U per ampoule.The purity of API B(candidate preparation)was not significantly decreased when it was placed at 4℃or 25℃,RH 80%for 10 d,and the purity was significantly decreased when it was exposed to light for 10 d.RSD of 15 API B(candidate standard)was 0.86%,showing good homogeneity.Conclusion:The first batch of national standard beinaglutide could be used for HPLC identification,content determination and biological activity determination of benalutide and related preparations of beinaglutide.

关 键 词：贝那鲁肽 标准品 结构确证 鉴别 含量测定 生物效价 质量平衡法 体外细胞培养法 

分 类 号：R917[医药卫生—药物分析学]