GC-MS/MS法测定阿加曲班中基因毒性杂质NDMA和NDEA
Determination of N-nitrosodimethylamine and N-nitrosodiethylamine in agatroban by GC-MS/MS
季行行 1刘芹 1邱荣英 1李铁健 1李观军 2张贵民3
作者信息
- 1. 山东新时代药业有限公司,山东 临沂 273400;国家手性制药工程技术研究中心,山东临沂 276005;山东省手性制药技术创新中心,山东 临沂 276005
- 2. 鲁南厚普制药有限公司,山东 临沂 276002
- 3. 鲁南制药集团股份有限公司,山东 临沂 276005;国家手性制药工程技术研究中心,山东临沂 276005;山东省手性制药技术创新中心,山东 临沂 276005
- 折叠
摘要
目的 采用GC-MS/MS法建立一种同时测定阿加曲班中N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)含量的方法.方法 以 Agilent DB-WAX UI(30 m×0.25 mm×0.25μm)气相色谱柱分离,离子源为电子轰击电离源(EI),在多反应离子监测(MRM)模式下检测,按外标法建立标准曲线测定阿加曲班中两种杂质的含量.结果 NDMA和NDEA分别在19.20～128.00 ng·mL-1和5.36～35.73 ng·mL-1与峰面积线性关系良好;NDMA和NDEA的定量限分别为19.20ng·mL-1和5.36 ng·mL-1,检测限分别为6.40 ng·mL-1和1.79 ng·mL-1.NDMA和NDEA低、中、高浓度的平均回收率分别为110.2％、107.8％、107.2％(RSD为 3.2％,n=3)和 114.7％、107.3％、107.6％(RSD为 5.6％,n=3).结论 该方法操作简单,能够有效测定阿加曲班中NDMA和NDEA的含量.
Abstract
Objective To simultaneously determine of N-nitrosodimethylamine(NDMA)and N-nitrosodiethylamine(NDEA)in agatroban by GC-MS/MS.Methods The sample was separated by Agilent DB-WAX UI chromatographic column(30 m×0.25 mm × 0.25 μm),while electron bombardment ionization source(EI)and the multiple reactive ion monitoring were selected for the dectection.A standard curve was established for the determination of both impurities in agatroban.Results NDMA and NDEA had good linearity at 19.20～128.00 ng·mL-1 and 5.36～35.73 ng·mL-1,respectively.The limit of quantification for NDMA and NDEA was 19.20 ng·mL-1 and 5.36 ng·mL-1.The limit of detection were 6.40 ng·mL-1 and 1.79 ng·mL-1,respectively.And the average recoveries of low,medium,and high concentration of NDMA and NDEA were 110.2％,107.8％,and 107.2％(RSD=3.2％,n=3),and 114.7％,107.3％,and 107.6％(RSD=5.6％,n=3),respectively.Conclusion This method is simple to operate,and can effectively detect the content of NDMA and NDEA in agatroban.
关键词
阿加曲班/GC-MS/MS法/N-亚硝基二甲胺/N-亚硝基二乙胺/多反应离子监测Key words
agatroban/GC-MS/MS/N-nitrosodimethylamine/N-nitrosodiethylamine/multiple reactive ion monitoring引用本文复制引用
出版年
2024
NETL
NSTL
万方数据