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
昝艳楠 1商少华 2陈宁 2丁逸梅1
作者信息
- 1. 南京工业大学药学院,南京 211816;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
- 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
- 折叠
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(30m×0.25 mm,0.25 μm);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1 μL.结果:NDMA的检测限为0.64 ng·mL-1,在4～16ng·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0.999 3.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.
Abstract
Objective:To establish a liquid-liquid extraction method for the determination of genotoxic impuri-ties 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,0.25 µm).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 1 µL.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 correla-tion r was 0.999 3.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 0.999 6.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Key words
gas chromatography-mass spectrometry/liquid-liquid extraction/genotoxic impurities/N-ni-trosodimethylamine/N-nitrosodimethylamine/chondroitin sulfate sodium引用本文复制引用
出版年
2024
NETL
NSTL
万方数据