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 of potential N-nitrosodimethylamine in azithromycin injections

目的探讨阿奇霉素注射剂中潜在N-亚硝胺的测定与风险。方法根据枣庄市食品药品检验检测中心依据美国食品药品管理局(FDA)、欧盟简介及欧洲药物管理局(EMA)所发行的相关指南,结合降解实验分析阿奇霉素结构及特点,并识别N-亚硝胺风险,明确控制限度,构建高效液相色谱串联质谱(HPLC-MS/MS),对阿奇霉素注射剂中的潜在N-亚硝胺实施测定。结果准确度:向供试品(批号:191013)中加入适量溶液,配置成为不同浓度(50%、100%、150%)水平的定限量(LOQ)溶液,回收率为85.9%~101.8%,平均回收率(n=12)为94.2%,回收率相对标准偏差(RSD)为5.4%。结论市面上阿奇霉素注射剂中的N-亚硝基二甲胺(NDMA)风险具有可控性,通过HPLC-MS/MS法检测可满足灵敏度的限定要求,且专属性回收率具有良好的回收度,便于各级质量检测机构对阿奇霉素中的NDMA风险作出精准评估,以此来强化质量,控制风险措施,同时也为监测化学合成药物中潜在N-亚硝胺的风险评估提供有效的鉴别基础。

Objective To explore the determination and risk of potential N-nitrosodimethylamine in azithromycin injection.Methods According to the Food and Drug Inspection and Testing Center of Zaozhuang City based on the relevant guidelines issued by US Food and Drug Administration(FDA)and European Medicines Agency(EMA),the structure and characteristics of azithromycin were analyzed in combination with degradation experiments,and the risk of N-nitrosamine was identified,the control limit was clearly defined.High performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was constructed to determine the potential N-nitrosodimethylamine in azithromycin injections.Results Accuracy:Appropriate amount of solution was added into the test product(batch number:191013)and configured as limit of quantification(LOQ)solution with different concentration levels(50%,100.00%,150.00%),and the recovery rate WAS 85.9%-101.8%,with an average(n=12)of 94.2%,and the relative standard deviation(RSD)was 5.4%.Conclusion The N-nitrosodimethylamine(NDMA)risk in azithromycin injection on the market is controllable,and HPLC-MS/MS detection can meet the limited requirements of sensitivity,and the specific recovery rate has a good recovery degree,which is convenient for quality testing institutions at all levels to accurately assess the NDMA risk in azithromycin,so as to strengthen quality control risk measures.At the same time,it also provides an effective identification basis for monitoring the potential risk assessment of N-nitrosodimethylamine in chemical synthesis.