气相色谱串联质谱法测定药用辅料中N-亚硝基二甲胺含量  

Content Determination of Genotoxic Impurity N-Nitrosodimethylamine in Pharmaceutical Excipients by Gas Chromatography-Tandem Mass Spectrometry

作　　者：韩勇 彭程 杨芳 王冉 薛雯 HAN Yong;PENG Cheng;YANG Fang;WANG Ran;XUE Wen(Jining Center for Food and Drug Control,Jining,Shandong,China 272071;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing,China 100700)

机构地区：[1]山东省济宁市食品药品检验检测研究院,山东济宁272071 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国药业》2021年第24期83-86,共4页China Pharmaceuticals

摘　　要：目的建立测定药用辅料中N-亚硝基二甲胺(NDMA)含量的气相色谱串联质谱法。方法色谱柱为Thermo TG-WAMS毛细管柱(30 m×0.25 mm,0.25μm),程序升温,流速为1.0 m L/min,载气为氦气,进样口温度为250℃;脉冲不分流进样,进样压力为12.285 psi,持续时间为0.5 min,进样量为1.5μL。离子源为电子轰击离子源,多反应监测模式。结果NDMA质量浓度在0.28~55.08 ng/m L范围内与峰面积线性关系良好(R^(2)=1.0000,n=9),检测限为0.11 ng/m L,定量限为0.28 ng/m L;精密度、稳定性、重复性试验的RSD均小于3.0%;平均加样回收率为95.05%,RSD为3.62%(n=9)。结论该方法操作简便,重复性好,准确度高,可用于测定药用辅料中NDMA的含量。Objective To establish a gas chromatography-tandem mass spectrometry(GC-MS/MS)method for the content determination of N-nitrosodimethylamine(NDMA)in pharmaceutical excipients.Methods The chromatographic column was Thermo TG-WAMS capillary column(30 m×0.25 mm,0.25μm)with temperature-programmed,the flow rate was 1.0 m L/min,the carrier gas was helium,the injection port temperature was 250℃.Pulse splitless injection technique was adopted,the injection pressure was 12.285 psi,the duration time was of 0.5 min,and the injection volume was 1.5μL.NDMA was ionized by electron ionization(EI),and detected with multiple-reaction monitoring(MRM)mode.Results The linear range of NDMA was 0.28-55.08 ng/m L(R^(2)=1.0000,n=9),the limit of detection(LOD)was 0.11 ng/m L and the limit of quantitation(LOQ)was 0.28 ng/m L.The RSDs of precision,stability and repeatability tests were less than 3.0%.The average recovery of NDMA was 95.05%with an RSD of 3.62%(n=9).Conclusion The method is simple,reproducible and accurate,which can be used for the content determination of NDMA in pharmaceutical excipients.

关 键 词：药用辅料 基因毒性杂质 N-亚硝基二甲胺 气相色谱串联质谱法 含量测定 

分 类 号：R927.2[医药卫生—药学]