GC-MS法测定酮咯酸氨丁三醇中的N-亚硝基吡咯烷、N-亚硝基吗啉和呋喃

Determination of N-Nitrosopyrrolidine,N-Nitrosomorpholine and Oxole in Ketorolac Tromethamine by GC-MS

建立了气相色谱-质谱(GC-MS)法测定酮咯酸氨丁三醇(1)中基因毒性杂质N-亚硝基吡咯烷(2)、N-亚硝基吗啉(3)和呋喃(4)的含量。采用ZB-1MS毛细管柱(30 m×0.25 mm×0.25μm),以多反应离子监测模式进行测定。结果显示,2、3、4分别在33.48~100.44、4.96~14.88、19.28~57.84 ng/ml内线性关系良好;定量限分别为25.11、3.72、14.46 ng/ml,检测限分别为8.54、1.26、4.92 ng/ml;平均回收率(n=9)分别为96.98%、98.17%、98.50%,RSD分别为5.42%、4.30%、1.93%。本研究可为1的质量控制研究提供参考。

A gas chromatography-mass spectrometry(GC-MS)method was established for the determination of genotoxic impurities,N-nitrosopyrrolidine(2),N-nitrosomorpholine(3)and oxole(4),in ketorolac tromethamine(1).A ZB-1MS capillary column(30 m×0.25 mm×0.25μm)was used for the determination in multiple reaction monitoring mode.The results showed that it was linear for 2,3 and 4 in the ranges of 33.48-100.44,4.96-14.88 and 19.28-57.84 ng/ml,respectively.The limits of quantification were 25.11,3.72,and 14.46 ng/ml,and the limits of detection were 8.54,1.26,and 4.92 ng/ml,respectively.The average recoveries(n=9)were 96.98%,98.17%,and 98.50%,with the RSDs of 5.42%,4.30%,and 1.93%,respectively.This study can provide a reference for the quality control of 1.