中国药物警戒 ›› 2021, Vol. 18 ›› Issue (5): 454-458.
DOI: 10.19803/j.1672-8629.2021.05.11

• 基础研究 • 上一篇    下一篇

液相-高分辨质谱技术测定盐酸二甲双胍缓释片中7种亚硝胺杂质的方法学研究

刘博, 张佟, 黄露, 张庆生*, 范慧红   

  1. 中国食品药品检定研究院,北京 102629; 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
  • 收稿日期:2019-12-10 出版日期:2021-05-15 发布日期:2021-05-12
  • 通讯作者: *张庆生,男,主任药师,食品药品安全。E-mail:zqs@nifdc.org.cn;#共同通信作者。
  • 作者简介:刘博,男,副研究员,药物分析。
  • 基金资助:
    北京市自然科学基金（7194337）

Determination of 7 N-nitrosoamines in Metformin Hydrochloride Sustained Release Tablets by LC-HRMS

LIU Bo, ZHANG Tong, HUANG Lu, ZHANG Qingsheng*, FAN Huihong   

  1. National Institutes for Food and Drug Control, Beijing 102629, China; NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, Beijing 102629, China
  • Received:2019-12-10 Online:2021-05-15 Published:2021-05-12

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摘要： 目的 建立液相-高分辨质谱联用（LC-HRMS）法测定盐酸二甲双胍缓释片中7种亚硝胺杂质的检测方法。方法 以十八烷基键合相硅胶为填料的色谱柱（100 mm×4.6 mm, 3 μm）;以0.1%甲酸-水为流动相A,0.1%甲酸-甲醇为流动相B,线性梯度洗脱;质谱采用电喷雾离子源,平行反应监测模式。结果 7种亚硝胺杂质在 1~100 ng/mL范围内线性关系良好;定量限在0.5~1 ng/mL之间;进样精密度RSD值在3.3%~7.4%之间;7种亚硝胺杂质的加样回收率在82.6%~111.4%的范围内。结论 该方法准确度和专属性好、灵敏度高,适用于盐酸二甲双胍缓释片中亚硝胺基因毒性杂质的检查与控制。

关键词: 盐酸二甲双胍缓释片, 亚硝胺, 高分辨质谱, 基因毒性, 质谱定量, 灵敏度

Abstract: Objective To establish an LC-HRMS method for determination of 7 N-nitrosoamines(7 NAs) genotoxic impurities in metformin hydrochloride sustained release tablets. Methods The separation was carried out on a C18 column (100 mm×4.6 mm, 3μm) by linear gradient elution using 0.1% formic acid as mobile phase A and 0.1% formic acid methanol as mobile phase B. The HRMS determination of NDMA was conducted by means of positive electrospray ionization parallel reactions monitoring. Results Linear calibrations were established for 7NAs in the range of 1 to 100 ng/mL. The limits of quantification ranged from 0.5 to 1 ng/mL while the average recovery ranged from 82.6% to 111.4%. Conclusion The established LC-HRMS method has proved to be suitable for the simultaneous quantitative determination of 7 NAs genotoxic impurities in metformin hydrochloride sustained release tablets.

Key words: metformin hydrochloride sustained release tablets, N-nitrosamine, HRMS, genotoxic impurities, quantitative analysis, sensitivity

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