药品质量标准中杂质的限度确定方式探讨  

Discussion on the determination of impurity limits in drug specification

作　　者：孙佳敏 杨美玲 杜颖 耿颖[2] 韩璐 刘万卉[1] 谭德讲[2] SUN Jia-min;YANG Mei-ling;DU Ying;GENG Ying;HAN Lu;LIU Wan-hui;TAN De-jiang(School of Pharmacy,Yantai University,Yantai 264003,China;NMPA Key Lab for Quality Research and Evaluation of Chemical Drug,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]烟台大学药学院,烟台264003 [2]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,中国食品药品检定研究院,北京102629

出　　处：《中国新药杂志》2023年第21期2129-2133,共5页Chinese Journal of New Drugs

基　　金：国家药品标准制修订课题(2022Y09);中检院质量安全与能力建设项目。

摘　　要：杂质限度范围的确立是药品质量标准建立的关键环节之一,合理的杂质限度对于药品的安全性和可控性至关重要,关系着药品的质量。本文以几种典型杂质为实例,系统阐述和演示了药品中杂质的每日最大暴露量(permitted daily exposure,PDE)的确定方式、在具体药品中的换算方式以及在产品中的限度确定方式,可更好地理解和实施ICH相关规范,为药品研发者对产品质量标准的制定提供参考。The establishment of impurity limits is one of the key factors in the establishment of drug product specifications.Reasonable impurity limits are very important for the safety and controllability,and closely related to the drug quality.Taking several typical impurities as examples,this paper systematically expounds and demonstrates the determination approach of the maximum daily exposure dose(PDE),the conversion method in specific drugs,and the limit determination of impurities in products,which can help better understand and implement ICH-related guidelines.This paper provides reference for drug developers to formulate product specification.

关 键 词：杂质限度 每日允许暴露量 残留溶剂 元素杂质 有害物质 最小能观察到效应/不良反应的药物剂量 最大无效应/不良反应的药物剂量 

分 类 号：R917[医药卫生—药物分析学]