中国药物警戒 ›› 2023, Vol. 20 ›› Issue (12): 1332-1338.
DOI: 10.19803/j.1672-8629.20230588

• 临床药物质量监测及评价专栏 • 上一篇    下一篇

HPLC-QE-MS技术分析盐酸倍他司汀注射液杂质谱及质量控制

王国英1, 周刚1△, 王勤1, 纪紫薇1, 宁霄2#, 崔黎1,*   

  1. 1内蒙古自治区药品检验研究院,内蒙古 呼和浩特 010020;
    2中国食品药品检定研究院食品化妆品检定所,北京100050
  • 收稿日期:2021-09-21 出版日期:2023-12-15 发布日期:2023-12-15
  • 通讯作者: *崔黎,女,本科,主任药师,药物质量标准研究。E-mail:413647638@qq.com; #为共同通信作者。
  • 作者简介:王国英,女,硕士,主管药师,化学药品（抗生素）检验及质量研究与评价。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2021YFC2401100）

Analysis of impurity spectra and quality control of betahistine hydrochloride injection based on HPLC-QE-MS technology

WANG Guoying1, ZHOU Gang1△, WANG Qin1, JI Ziwei1, NING Xiao2#, CUI Li1,*   

  1. 1Inner Mongolia Institute of Drug Inspection, Hohhot, Inner Mongolia 010020, China;
    2Institute for Food and Cosmetics Testing, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2021-09-21 Online:2023-12-15 Published:2023-12-15

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摘要： 目的 通过对盐酸倍他司汀注射液杂质谱进行研究,为该品种质量控制提供依据。方法 采用高效液相-高分辨质谱（HPLC-QE-MS）技术,对盐酸倍他司汀注射液中各杂质结构进行解析并分析其裂解规律,结合强制降解试验,对各个杂质进行归属并建立杂质谱;采用ADMET Predictor软件,预测各杂质的基因毒性。结果 建立的有关物质测定方法,专属性、准确度、精密度、耐用性良好;通过高分辨质谱共确证4个未知杂质和3个已知杂质,其中杂质1、2、3均为工艺杂质,杂质A、B和杂质4均为降解杂质,杂质C为工艺和降解杂质。毒性预测结果显示,杂质1、杂质2、杂质3具有潜在的大鼠急性毒性;杂质A、杂质B、杂质1、杂质4具有潜在的肝脏毒性;对杂质谱及灭菌工艺进行相关性分析,盐酸倍他司汀对热不稳定,目前各企业使用的灭菌工艺会使有关物质数量和含量增加。结论 通过对盐酸倍他司汀注射液杂质谱研究,推测各杂质的来源、结构及其毒性,通过对杂质谱及灭菌工艺进行相关性分析,为优化生产工艺及质量控制提供依据。

关键词: 盐酸倍他司汀, 注射液, 杂质谱, 基因毒性, 高效液相-高分辨质谱, 质量控制, 方法学

Abstract: Objective To analyze the impurity spectra of betahistine hydrochloride injection to provide a basis for quality control of this variety. Methods HPLC-QE-MS technology were applied to identify and analyze the structure of an unknown impurity of betahistine hydrochloride injection. According to forced degradation test, the source of impurities and impurity spectra were determined. ADMET Predictor software was used to predict the toxicity of impurities. Results The method established for related substances was simple with high accuracy and good reproducibility, total of four unknown impurities were detected, Impurities 1, 2, and 3 were all process impurities, impurities A, impurities B, and impurities 4 were all degradation impurities, and impurity C was both process and degradation impurity. The toxicity prediction results showed that impurity 1, 2, and 3 had potential acute toxicity in rats; Impurities A, B, 1, and 4 had potential liver toxicity. Correlation analysis of impurity mass spectrometry and sterilization process showed that betahistine hydrochloride was thermally unstable, and the sterilization process currently used by various enterprises would increase the quantity and content of related substances. Conclusion By studying the impurity mass spectrometry of betahistine hydrochloride inject

Key words: betahistine hydrochloride injection, impurity spectrum, genetic toxicity, HPLC-QE-MS, quality control, methodology

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