阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析  

Determination and risk analysis for potential N-nitrosamines in azithromycin injection

作　　者：吴杨 许奇 钱岩 黄逸文 WU Yang;XU Qi;QIAN Yan;HUANG Yi-wen(Suzhou Institute for Drug Control,Suzhou Centre of Adverse Drug Reaction Monitoring,Suzhou 215000,China)

机构地区：[1]苏州市药品检验检测研究中心苏州市药品不良反应监测中心,苏州215000

出　　处：《中国新药杂志》2021年第21期1998-2002,共5页Chinese Journal of New Drugs

摘　　要：目的:识别阿奇霉素中潜在N-亚硝胺风险,并建立相应测定方法进行确认性检测,为生产企业开展风险评估提供借鉴。方法:按照美国FDA、欧洲EMA发布的相关指南,基于阿奇霉素结构特点与合成工艺,结合降解实验,对其中可能存在的N-亚硝胺风险进行识别,确定控制限度,并建立相应的HPLC-MS/MS法,对15个厂家的61批阿奇霉素注射剂中潜在N-亚硝基二甲胺(NDMA)含量进行确认性检测。结果:阿奇霉素有由原料直接引入或氧化降解生成NDMA的风险;实际收集的61批样品中NDMA含量均低于定量限。结论:市面上阿奇霉素注射剂中NDMA风险可控;建立的HPLC-MS/MS法灵敏度满足限度要求,专属性回收率精密度良好,可用于生产企业对阿奇霉素中NDMA风险评估的确认性检测与质量控制,也可为其他化学合成药品中潜在N-亚硝胺风险评估与测定提供借鉴。Objective:To identify the potential risk of N-nitrosamines in azithromycin and to establish corresponding method for confirmatory testing,providing reference for risk assessment by manufacturers.Methods:In conformity with the relevant industry guidance of FDA and EMA,risk identification and control limits for potential N-nitrosamines in azithromycin was conducted based on the structure and synthetic route,as well as degradation test.A liquid chromatography-mass spectrometry method was subsequently established and applied to the confirmatory testing of N-nitrosodimethylamine in azithromycin injection of 61 batches from 15 different manufacturers.Results:N-nitrosodimethylamine was probably introduced from starting material or generated as the degradation product of azithromycin.In all cases,N-nitrosodimethylamine were found below the limit of quantitation.Conclusion:The risk of potential N-nitrosamines in azithromycin injection was acceptable.This method proved sensitive,selective,accurate and suitable to the confirmatory testing and quality control of N-nitrosodimethylamine in azithromycin injection.The article also provided an example to the risk assessment and confirmatory testing of potential N-nitrosamines in chemically synthesized APIs and drug products.

关 键 词：N-亚硝胺 阿奇霉素注射剂 HPLC-MS/MS 风险分析 

分 类 号：R917[医药卫生—药物分析学]