中国药物警戒 ›› 2023, Vol. 20 ›› Issue (4): 370-373.
DOI: 10.19803/j.1672-8629.20230071

• 前沿分析方法在药品质量评价中的应用专栏 • 上一篇    下一篇

琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质含量测定研究

刘春亮1, 刘小琼2, 张磊1, 朱克旭1, 曹杰永3, 王晨4#, 许明哲4,*, 张现化5   

  1. 1滁州市食品药品检验中心,安徽 滁州 239000;
    2安徽省药品审评查验中心,安徽 合肥 230051;
    3合肥合源药业有限公司,安徽 合肥 230088;
    4中国食品药品检定研究院,北京 100050;
    5北京大学第三医院药剂科,北京 100191
  • 收稿日期:2023-02-13 出版日期:2023-04-15 发布日期:2023-04-20
  • 通讯作者: *许明哲,男,博士,主任药师,药物质量评价与药事管理。E-mail：xumzhe@nifdc.org.cn;#为共同通信作者。
  • 作者简介:刘春亮,男,本科,副主任药师,药品检验。
  • 基金资助:
    国家重点研发计划（SQ2022YFC3401205）

Determination of ethylene oxide genotoxic impurity in metoprolol succinate

LIU Chunliang1, LIU Xiaoqiong2, ZHANG Lei1, ZHU Kexu1, CAO Jieyong3, WANG Chen4#, XU Mingzhe4,*, ZHANG Xianhua5   

  1. 1Chuzhou Institute for Food and Drug Control, Chuzhou Anhui 239000, China;
    2Anhui Center for Drug Evaluation& Inspection, Hefei Anhui 230051, China;
    3Hefei Cosource Pharmaceuticals Inc, Hefei Anhui 230088, China;
    4National Institutes for Food and Drug Control, Beijing 100050, China;
    5Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
  • Received:2023-02-13 Online:2023-04-15 Published:2023-04-20

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摘要： 目的 对琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质含量进行测定。方法 采用高效液相色谱法测定琥珀酸美托洛尔中含有环氧乙烷结构的杂质XI含量。色谱柱采用Wondasil C18-WR柱（250 mm×4.6 mm, 5.0 μm）,以流动相A为缓冲液（取磷酸二氢钾2.72 g,高氯酸钠一水合物6.13 g,加水1 000 mL溶解后,用1.0 mol·L-1氢氧化钠溶液调pH值至6.0）,流动相B为甲醇的梯度洗脱,流速1.0 mL·min-1,进样量40 μL,柱温30℃,检测波长280 nm。结果 杂质XI在线性范围为0.852 3~6.818 3 μg·mL-1内,r=0.999 9,检测限浓度为0.426 1 μg·mL-1,定量限浓度为0.852 3 μg·mL-1,平均回收率为94.21%。结论 本研究准确可靠、专属性强且重现性好,可为琥珀酸美托洛尔中潜在的环氧乙烷类基因毒性杂质的质量控制和安全性评价提供科学依据。

关键词: 琥珀酸美托洛尔, 环氧乙烷类, 基因毒性, 杂质, 梯度洗脱, 含量测定, 高效液相色谱法, 专属性

Abstract: Objective To establish an HPLC method for the determination of ethylene oxide genotoxic impurity XI in metoprolol succinate. Methods The Wondasil C18-WR (4.6 mm×250 mm, 5.0 μm) column was used. The mobile phase consisted of methanol and buffer (potassium dihydrogen phosphate 2.72 g, sodium perchlorate monohydrate 6.13 g, dissolved in 1 000 mL water, with pH adjusted to 6.0 with 1. 0 mol·L-1 sodium hydroxide solution) under gradient elution. The flow rate was 1.0 mL·min-1, the injection volume was 40 μL, the column temperature was 30℃ and the detection wavelength was 226 nm. Results The linear range of impurity XI was 0.853 2 to 6.818 3 μg·mL-1(r=0.999 9). The detection limit was 0.426 1 μg·mL-1, with a quantitative limit of 0.852 3 μg·mL-1. The average recovery was 94.21%. Conclusion This method is highly specific, sensitive and user-friendly, which can be used for the determination of genotoxic impurity of ethylene oxide in metoprolol succinate.

Key words: metoprolol succinate, ethylene oxide derived glycol ethers, genotoxic, impurity, gradient elution, content determination, high performance liquid chromatography( HPLC), highly specific

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