药品中亚硝胺类杂质分析方法研究进展

李昊; 刘士峰; 孙彩霞; 张帅; 齐前程

doi:10.2095-3593.2026.050012

中国药物评价 >

2026 , Vol. 43 >Issue 3: 170 - 170-176

DOI: https://doi.org/10.2095-3593.2026.050012

评价技术与方法

药品中亚硝胺类杂质分析方法研究进展

李昊 ,
刘士峰 ,
孙彩霞 ,
张帅 ,
齐前程

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1.青岛国信制药有限公司，山东青岛 266000；
2.安丘市检验检测中心有限公司，山东潍坊 262100；
3.潍坊食品科技职业学院食品与生物工程学院，山东潍坊 262100

李昊，男，工程师，研究方向：药物分析

收稿日期: 2025-12-31

修回日期: 2026-03-17

录用日期: 2026-05-19

网络出版日期: 2026-08-12

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Research Progress on Analytical Methods for Nitrosamine Impurities in Pharmaceutical Products

Michael Lee

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1.Qingdao Guoxin Pharmaceutical Co.， Ltd.，Shandong Qingdao 266000，China；
2.Anqiu Inspection and Testing Center Co.， Ltd.， Shandong Weifang 262100， China；
3.Weifang Vocational College of Food Science and Technology， School of Food and Biology Engineering， Shandong Weifang 262100， China

Received date: 2025-12-31

Revised date: 2026-03-17

Accepted date: 2026-05-19

Online published: 2026-08-12

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摘要

基因毒性杂质被公认具有致突变性和致癌性、对DNA造成极大损伤、严重危害生命健康的物质。亚硝胺类杂质作为基因毒性杂质中具有高致癌风险的“关注队列”杂质，成为研究热点之一。本研究阐述药品中亚硝胺类杂质分类和形成机制，包括小分子亚硝胺类杂质和亚硝胺类原料药相关杂质（NDSRI）以及此类杂质的限度制定依据；总结药品领域亚硝胺类杂质分析方法研究进展，包括前处理方法和定量方法，前处理方法主要包括用溶剂直接溶解、过滤、离心、萃取、超声；定量方法常见的有气相色谱法、液相色谱法、气质联用法和液质联用法。另外，NDSRI作为一类特别的亚硝胺类杂质，近年来受到高度关注，本研究介绍此类杂质分析方法的研究进展，旨在为药品领域研究者在起始物料、中间体、原料药、辅料、包材、制剂中进行亚硝胺类杂质分析方法选择、开发和验证提供思路。

关键词： ; font-size:medium; "> ; 基因毒性杂质；亚硝胺类杂质；分析方法；亚硝胺类原料药相关杂质；药品安全

本文引用格式

李昊 , 刘士峰 , 孙彩霞 , 张帅 , 齐前程 . 药品中亚硝胺类杂质分析方法研究进展[J]. 中国药物评价, 2026 , 43(3) : 170 -170-176 . DOI: 10.2095-3593.2026.050012

Abstract

Genotoxic impurities are generally acknowledged to have mutagenicity and carcinogenicity， which can cause great damage to DNA. Furthermore， it can seriously endanger the life health of human. Nitrosamine impurities， as the “cohort of concern” impurities of genotoxic impurities， which possesses significant carcinogenic risk， have become one of the research hotspots. This study introduces the categories and formation mechanisms of nitrosamine impurities including small molecular nitrosamine impurities and nitrosamine drug substance related impurities(NDSRI)， and basis for limit establishment of this kind of impurities， and also summarizes the research progress of analytical methods for nitrosamine impurities in pharmaceutical area， including pre-treatment methods and quantitative methods. Pre-treatment methods mainly includes direct dissolution by solvents， filtration， centrifugation， extraction and ultrasonication. Common quantitative methods include gas chromatography， liquid chromatography， gas chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. In addition， NDSRI， as a special kind of nitrosamine impurities， has been highly concerned in recent years. This study introduces the research progress of analytical methods for this kind of impurities individually， in order to provide references for researchers about the selection， development and validation of analytical methods for nitrosamine impurities in pharmaceutical field， such as starting materials， intermediates， drug substances， ingredients， packaging materials and drug products.

Key words： ; font-size:medium; ">Genotoxic impurities； Nitrosamine impurities； Analytical methods； Nitrosamine drug substance related impurities (NDSRI)； Drug safety

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