中国药物警戒 ›› 2023, Vol. 20 ›› Issue (12): 1339-1345.
DOI: 10.19803/j.1672-8629.20230592

• 临床药物质量监测及评价专栏 • 上一篇    下一篇

HPLC-QE-MS技术开展注射用腺苷钴胺有关物质研究

郝钢1, 韩峰1△, 周刚1, 颜皓1, 武星1, 李旭扬1, 候海玲1, 宁霄2, 汪祺3#, 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;
    3中国食品药品检定研究院中药民族药检定所，北京 100050
  • 收稿日期:2023-09-21 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:郝钢,男,硕士,副主任药师,药理学与药物安全性评价。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2021YFC2401100）

Research on the related substances of adenosine cobalt amine for injection based on HPLC-QE-MS technology

HAO Gang1, HAN Feng1△, ZHOU Gang1, YAN Hao1, WU Xing1, LI Xuyang1, HOU Hailing1, NING Xiao2, WANG Qi3#, 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;
    3Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2023-09-21 Online:2023-12-15 Published:2023-12-15

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摘要： 目的 采用高效液相色谱法开展注射用腺苷钴胺有关物质研究,并对相关杂质进行质谱分析和毒性预测。方法 高效液相色谱法测定,色谱条件是用十八烷基硅烷键合硅胶为填充剂色谱柱,检测波长为260 nm,柱温35℃,进样体积10μL,0.01 mol·L-1酸铵溶液（冰醋酸调剂pH值至4.0）为流动相A,甲醇为流动相B,进行梯度洗脱。采用所建方法对105批注射用腺苷钴胺开展有关物质评价。含量≥0.1%的未知杂质采用高效液相色谱串联四极杆静电场轨道阱高分辨质谱（HPLC-QE-MS）扫描并对未知杂质开展基因毒性预测。结果 所建方法各杂质峰能与主峰有效分离,检测限为1.497×10-4 mg·mL-1,对检测方法进行了方法学验证,结果符合药典要求。结论 所建方法测定专属性强,准确度高,重复性好,能够有效获得全面的杂质信息,适用于注射用腺苷钴胺的杂质检查与控制。

关键词: 注射用腺苷钴胺, 有关物质, 高效液相色谱, 质谱, 杂质, 方法学

Abstract: Objective High performance liquid chromatography was used to study the related substances of adenosine cobalt amine for injection, and mass spectrometry analysis and toxicity prediction were performed on the related impurities. Methods Determination by high-performance liquid chromatography, the chromatographic conditions were using octadecylsilane bonded silica gel as the filling agent in the chromatographic column, with a detection wavelength of 260 nm, a column temperature of 35℃, and an injection volume of 10 μL. 0.01 mol·L-1 ammonium acetate solution (adjusted to pH 4.0 with glacial acetic acid) was used as mobile phase A, and methanol was used as mobile phase B for gradient elution. The established method was used to evaluate the related substances in 105 batches of adenosine cobalt amine for injection. Unknown impurities with a content of ≥0.1% were scanned by high-resolution mass spectrometry and genotoxicity prediction was performed on the unknown impurities. Results The impurity peaks of the established method were effectively separated from the main peak, with a detection limit of 1.497×10-4 mg·mL-1. The methodological validation of the detection method was conducted, and the results met the requirements of the pharmacopoeia. Conclusion The established method has strong specificity, high accuracy, good repeatability, and can effectively obtain comprehensive impurity information. It is suitable for impurity detection and control of adenosine cobalt amine for injection.

Key words: adenosine cobalt amine for injection, related substances, high-performance liquid chromatography, mass spectrometry, impurity, methodology

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