中国新药杂志

化学药品中亚硝胺杂质风险评估与控制体系的构建及应用

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邵方娴 ¹^,² , 芦丽 ¹^,² , 黄朝瑜 ¹^,² , 许慧 ¹^,² , 李睿 ¹^,²^,^* , 严菲 ¹^,²^,^*

中国新药杂志 | 实验研究 2026,35(19): 2120-2128

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中国新药杂志 |实验研究 2026 , 35 (19) : 2120 -2128

化学药品中亚硝胺杂质风险评估与控制体系的构建及应用

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邵方娴¹^,², 芦丽¹^,², 黄朝瑜¹^,², 许慧¹^,², 李睿¹^,²^,^*, 严菲¹^,²^,^*

作者信息

¹江苏省药品监督检验研究院，南京 210019

²国家药品监督管理局监管科学创新研究基地，南京 210019

通讯作者:

李睿，女，主任药师，主要从事药物质量管理工作。E-mail: 910768507@qq.com。

严菲，女，主任药师，主要从事药物分析工作。E-mail: 37931658@qq.com。

作者简介:

邵方娴，女，副主任药师，主要从事药物分析工作。E-mail: medicine-sfx@163.com。

Establishment of a risk assessment and control system for nitrosamine impurities in chemical drugs and its application

Fang-xian SHAO¹^,², Li LU¹^,², Chao-yu HUANG¹^,², Hui XU¹^,², Rui LI¹^,²^,^*, Fei YAN¹^,²^,^*

Affiliations

1 Jiangsu Institute for Drug Control, Nanjing 210019, China

2 NMPA Center for Innovation and Research in Regulatory Science, Nanjing 210019, China

出版时间: 2026-10-15 doi: 10.20251/j.cnki.1003-3734.2026.19.014

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摘要

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目的：

构建化学药品中亚硝胺杂质风险评估与控制体系，并用于盐酸普萘洛尔片中亚硝胺杂质的研究。

方法：

检索各国药品监管机构、PubMed、Elsevier和Wiley网站，对亚硝胺杂质产生机制、毒性评估和控制措施进行分析总结，对药品中亚硝胺杂质风险评估与控制的指导原则进行梳理。

结果：

从亚硝胺杂质风险评估要素、杂质限度的确定、确认性检测以及过程控制要素4个方面构建了亚硝胺杂质风险评估与控制体系，并应用于盐酸普萘洛尔片中亚硝胺杂质的评估，采用鱼骨分析法从盐酸普萘洛尔片的原料、辅料、工艺过程和贮存等方面分析亚硝胺杂质风险因素，对抽检样品及其原料进行测定，结合原辅料相容性、影响因素和加速稳定性试验初步探究影响亚硝胺杂质产生的因素并提出控制措施。

结论：

构建的化学药品中亚硝胺杂质风险评估与控制体系有助于药品中亚硝胺杂质控制策略的制定，也为监管部门及制药企业实施亚硝胺杂质风险精准控制提供技术参考。

关键词

化学药品 / 亚硝胺杂质 / 风险评估与控制体系 / 盐酸普萘洛尔片

Abstract

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Objective:

To establish a risk assessment and control system for nitrosamine impurities in chemical drugs and apply it to the study of nitrosamine impurities in propranolol hydrochloride tablets.

Methods:

Information was retrieved from various national drug regulatory agencies, PubMed, Elsevier and Wiley websites, and the formation mechanisms, toxicity assessment, and control measures of nitrosamine impurities were analyzed and summarized. Guidelines for risk assessment and control of nitrosamine impurities in pharmaceuticals were systematically reviewed.

Results:

A risk assessment and control system for nitrosamine impurities was constructed, covering four key aspects: risk assessment elements, determination of impurity limits, confirmatory testing, and process control factors. This system was applied to evaluate nitrosamine impurities in propranolol hydrochloride tablets. Using fishbone diagram analysis, risk factors for nitrosamine impurities were identified from aspects such as active ingredients, excipients, manufacturing processes, and storage conditions of the tablets. Samples from market surveillance and their raw materials were tested. Factors influencing the formation of nitrosamine impurities were preliminarily investigated through excipient compatibility studies, stress testing, and accelerated stability testing, and corresponding control measures were proposed.

Conclusion:

The established risk assessment and control system for nitrosamine impurities in pharmaceuticals will aid in the development of strategies for managing these impurities. It also provides technical references for regulatory authorities and pharmaceutical companies to implement precise control of nitrosamine-related risks.

Key words

chemical drug / nitrosamine impurities / risk assessment and control system / propranolol hydrochloride tablets

引用本文

邵方娴, 芦丽, 黄朝瑜, 许慧, 李睿, 严菲. 化学药品中亚硝胺杂质风险评估与控制体系的构建及应用. 中国新药杂志, 2026 , 35 (19) : 2120 -2128 . DOI: 10.20251/j.cnki.1003-3734.2026.19.014

Fang-xian SHAO, Li LU, Chao-yu HUANG, Hui XU, Rui LI, Fei YAN. Establishment of a risk assessment and control system for nitrosamine impurities in chemical drugs and its application[J]. Chinese Journal of New Drugs, 2026 , 35 (19) : 2120 -2128 . DOI: 10.20251/j.cnki.1003-3734.2026.19.014

基金

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2024年国家药品抽检计划资助项目(国药监药管〔2024〕1号)

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2026年第35卷第19期

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文章信息

doi: 10.20251/j.cnki.1003-3734.2026.19.014

接收时间：2025-12-01
首发时间：2026-10-29
出版时间：2026-10-15

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出版历史

收稿日期：2025-12-01

基金

2024年国家药品抽检计划资助项目(国药监药管〔2024〕1号)

作者信息

¹江苏省药品监督检验研究院，南京 210019

²国家药品监督管理局监管科学创新研究基地，南京 210019

通讯作者:

李睿，女，主任药师，主要从事药物质量管理工作。E-mail: 910768507@qq.com。

严菲，女，主任药师，主要从事药物分析工作。E-mail: 37931658@qq.com。

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https://castjournals.cast.org.cn/joweb/zgxyzz/CN/10.20251/j.cnki.1003-3734.2026.19.014

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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