化学药品中杂质的基因毒性评估策略以及相关分析方法研究进展  

Strategies for genotoxicity assessment and advances in analytical techniques of impurities of chemical drugs

作　　者：万君玥 陈华[2] 尹婕[2] WAN Jun-yue;CHEN Hua;YIN Jie(China Pharmaceutical University,Nanjing 210009,China;National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国药科大学,南京210009 [2]中国食品药品检定研究院,北京102629

出　　处：《药物分析杂志》2022年第4期557-571,共15页Chinese Journal of Pharmaceutical Analysis

摘　　要：基因毒性杂质是受到药品监管机构和制药企业重点关注和控制的对象,由于其较一般杂质具有微量水平就存在潜在致突变性和致癌性风险的特点,需要严格控制其在药物中的含量以保证药物质量与临床应用的安全性。本文从识别警示结构、文献及数据库检索、量化构效关系软件预测、体内外遗传毒性试验、依照法规和指南要求制定合理限度等方面综述了评估杂质基因毒性的研究策略,并总结了目前为了应对其含量低,稳定性较差,结构多样等特点开发的各类前处理技术及分析方法,为基因毒性杂质的研究提供参考。Genotoxic impurities(GTIs)are of increasing concerns to both regulatory agencies and pharmaceutical industries due to their potentials for mutagenesis and carcinogenesis,and theyneed to be strictly controlled to ensure the quality and safety in pharmaceuticals.This article provides the research strategies for assessment of GTIs from the following points,involving identification of structural alerts,literature&database retrieval,in silico(quantitative)structure-activity relationship models/systems,genetic toxicity test and the establishment of appropriate acceptable limit.This article also summarizes the recent advances in sample pre-treatment technologies and analytical methods for trace levels of GTIs,which provides reference for research of GTIs.

关 键 词：基因毒性杂质 警示结构 量化构效关系 遗传毒性试验 限度 前处理 分析方法 

分 类 号：R917[医药卫生—药物分析学]