利福平和利福喷丁中亚硝胺类杂质控制策略综述

Control strategies for nitrosamine impurities in rifampin and rifapentin

本文综述了国外药品监管机构美国FDA、WHO、欧洲EMA对利福平中亚硝胺类杂质1-甲基-4-亚硝基哌嗪(MNP)和利福喷丁中1-环戊基-4-亚硝基哌嗪(CPNP)控制策略,旨在为我国药品监管机构和药品上市许可持有人制定这2种药物中亚硝胺类杂质的控制限度提供参考。同时,对利福平和利福喷丁中亚硝胺类杂质的产生原因、每日可接受摄入量、检测方法进行分析,探讨降低药品中杂质含量的方法;借鉴国外监管机构经验,对我国制订2种药物中亚硝胺类杂质的防控措施提出意见和建议。

This article reviews the control strategies of the nitrosamine impurities,such as 1⁃methyl⁃4⁃nitrosopiperazine(MNP)in rifampin and 1⁃cyclopentyl⁃4⁃nitrosopiperazine(CPNP)in rifapentine by FDA,WHO and EMA,in order to to provide a reference for Chinese drug regulatory agency and Marketing Authorization Holder to establish the control limit of nitrosamine impurities in the two drugs.Meanwhile,the cause,acceptable limits and detection methods of nitrosamine impurities in rifampin and rifapentine are analyzed,and the methods of reducing the content of the impurities are discussed.Referring to the experience of foreign regulatory agencies,suggestions are put forward on the prevention and control measures of nitrosamine impurities in the two tuberculosis drugs in China.