中国药物警戒 ›› 2026, Vol. 23 ›› Issue (5): 500-505.
DOI: 10.19803/j.1672-8629.20260290

• 亚硝胺类药物相关杂质安全性研究专栏 • 上一篇    下一篇

亚硝胺类药物相关杂质合成研究进展

靳龙龙1, 文海若2,3, 杨会英1, 王青1, 邵长军1, 吴先富1,*   

  1. 1中国食品药品检定研究院标准物质和标准化管理中心,北京 102629;
    2中国食品药品检定研究院安全评价研究所,北京 100176;
    3药品监管科学全国重点实验室,北京 102629
  • 收稿日期:2026-04-09 发布日期:2026-05-20
  • 通讯作者: *吴先富,男,博士,研究员,标准物质研究与药品质量控制。E-mail: wuxf99@163.com
  • 作者简介:靳龙龙,男,博士,助理研究员,标准物质合成与药品质量控制。
  • 基金资助:
    国家自然科学基金资助项目（82473889）; 药品监管科学全国重点实验室课题“药品杂质遗传毒性评价新技术和生物标志物研究”（2023SKLDRS0128）

Research Progress in Nitrosamine Drug Substance-Related Impurity Synthesis

JIN Longlong1, WEN Hairuo2,3, YANG Huiying1, WANG Qing1, SHAO Changjun1, WU Xianfu1,*   

  1. 1Center of Reference Standards and Standardization, National Institutes for Food and Drug Control, Beijing 102629, China;
    2Institute of Safety Evaluation, National Institutes for Food and Drug Control, Beijing 100176, China;
    3State Key Laboratory of Drug Regulatory Science, Beijing 102629, China
  • Received:2026-04-09 Published:2026-05-20

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摘要： 目的 介绍多种类型亚硝胺类药物相关杂质的合成方法,为其分析方法开发、遗传毒性评价以及制定更加科学合理的限值所需相应对照品的合成提供参考。方法 通过查阅文献以及合成实验总结,梳理亚硝胺类药物相关杂质的合成方法及研究进展。结果 当前关于亚硝胺类药物相关杂质合成方法的文献报道相对较少,部分亚硝胺类药物相关杂质的合成仍面临着诸多技术难题和挑战。本文分类归纳了直接合成法、间接合成法及多种合成策略,解决了部分难合成的亚硝胺类药物相关杂质的合成难题。结论 鉴于部分亚硝胺类药物相关杂质的合成仍然存在一定难度,需进行深入研究,以保证相应原料药及其制剂检验检测所需对照品的可获得性,从而服务于药品监管。

关键词: 亚硝胺类药物相关杂质, 遗传毒性, 合成, 药品监管, 研究进展

Abstract: Objective To introduce the synthetic methods of various nitrosamine drug substance-related impurities (NDSRIs) in order to provide a reference for the preparation of their reference standards for the development of analytical methods, evaluation of genetic toxicity, and for setting better limits. Methods The synthetic methods of and research progress in NDSRIs were outlined based on related literature and synthetic experiments. Results There were relatively few literature reports on the synthetic methods of NDSRIs, and many technological difficulties and challenges persisted. In this article, direct and indirect synthetic methods as well as multiple synthetic strategies were classified and summarized while solutions to the synthesis of some of the difficult-to-synthesize NDSRIs were recommended. Conclusion The technical challenges facing the synthesis of some NDSRIs require the availability of reference standards needed for the inspection and testing of the corresponding APIs and their preparations so as to facilitate the regulation of drugs.

Key words: Nitrosamine Drug Substance-Related Impurities (NDSRIs), Genotoxicity, Synthesis, Drug Regulation, Research Progress

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