液液萃取/GC-MS法测定硫酸软骨素钠原料中的基因毒杂质N-亚硝基二甲胺与N-亚硝基二乙胺  

Determination of genotoxic impurities N-nitrosodimethylamine and N-nitrosodiethylamine in chondroitin sulfate sodium raw materials by liquid-liquid extraction/GC-MS

作　　者：昝艳楠 商少华 陈宁 丁逸梅[1,2] ZAN Yan-nan;SHANG Shao-hua;CHEN Ning;DING Yi-mei(Shool of Pharmacy,Nanjing University of Technology,Nanjing 211816,China;Jiangsu Pharmaceutical Research Institute Co.,Ltd.,Drug Testing and Packaging Materials Research Center,Nanjing 210009,China)

机构地区：[1]南京工业大学药学院,南京211816 [2]江苏药物研究所有限公司药品检测与包材研究中心,南京210009

出　　处：《药物分析杂志》2024年第3期462-467,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立一种液液萃取法,采用气相色谱-质谱联用(GC-MS)技术,测定硫酸软骨素钠原料中的基因毒杂质N-亚硝基二甲胺(NDMA)与N-亚硝基二乙胺(NDEA)。方法:采用Thermo TG-WAXMS色谱柱(30 m×0.25 mm,0.25μm);柱温在40℃保持1 min,以25℃·min^(-1)升至240℃,保持2 min;进样口温度为220℃;载气为高纯氦,流速为1.0 mL·min^(-1)。质谱的离子源为EI源;电子能量为70 eV;离子源温度为280℃;传输线温度为240℃;进样量为1μL。结果:NDMA的检测限为0.64 ng·mL^(-1),在4~16 ng·mL^(-1)范围内峰面积与浓度呈良好的线性关系,相关系数r为0.9993。NDEA的检测限为0.176 ng·mL^(-1),在1.1~4.4 ng·mL^(-1)范围内峰面积与浓度呈良好的线性关系,相关系数r为0.9996。硫酸软骨素钠中均未检出NDMA与NDEA。结论:该法操作简便,专属性强,可以用于硫酸软骨素钠中的基因毒杂质NDMA与NDEA的测定。Objective:To establish a liquid-liquid extraction method for the determination of genotoxic impurities N-nitrosodimethylamine(NDMA)and N-nitrosodiethylamine(NDEA)in chondroitin sulfate sodium by gas chromatography-mass spectrometry(GC-MS).Methods:The chromatographic column was Thermo TG WAXMS(30 m×0.25 mm,0.25μm).The column temperature was maintained at 40℃for 1 min,increased to 240℃at 25℃·min^(-1)and maintained for 2 min.The inlet temperature was 220℃.The carrier gas was high-purity helium,and the flow rate was 1.0 mL·min^(-1).The ion source of mass spectrometry was EI source.The electron energy was 70 eV.The ion source temperature was 280℃and the transmission line temperature was 240℃.Injection volume was 1μL.Results:The LOD of NDMA was 0.64 ng·mL^(-1).Experiment showed a good linear relationship between peak area and concentration in the range of 4-16 ng·mL^(-1),and the correlation r was 0.9993.The LOD of NDEA was 0.176 ng·mL^(-1)with a good linear relationship between peak area and concentration within the range of 1.1-4.4 ng·mL^(-1).The correlation r was 0.9996.NDMA and NDEA were not detected in chondroitin sulfate sodium.Conclusion:The method is simple,specific and can be used to determine the genotoxic impurities NDMA and NDEA in chondroitin sulfate sodium.

关 键 词：气相色谱-质谱法 液液萃取 基因毒杂质 N-亚硝基二甲胺 N-亚硝基二乙胺 硫酸软骨素钠 

分 类 号：R917[医药卫生—药物分析学]