顶空气相色谱法测定头孢氨苄原料中的残留N,N-二甲基甲酰胺

Headspace GC method determination of residual N,N-dimethylformanide in cefalexin drug substance

目的:建立头孢氨苄原料药中残留N,N-二甲基甲酰胺残留量的检测方法。方法:采用DB-624毛细管色谱柱(30m×0.32mm×1.8μm),载气为氮气,样品溶剂为1,3-二甲基咪唑啉酮(1,3-dimethylim idazolidinone),顶空进样,进样口温度为200℃,程序升温,进样分流比为1:5,氢火焰离子化检测器(FID),检测器温度为250℃。结果:N,N-二甲基甲酰胺浓度在12.38～247.7μg.mL-1范围内线性关系良好(r=0.9998),检测限(信噪比3:1)和定量限(信噪比10:1)分别为3.83和11.48μg.mL-1,精密度、重复性以及耐用性的RSD均小于4%,N,N-二甲基甲酰胺3个浓度水平(50%,100%,120%)的回收率(n=3)在85.7%～89.2%之间,平均回收率(n=9)为86.9%。结论:所建立的方法简单,操作方便,专属性强,重现性好,灵敏度高,能够准确地测定头孢氨苄原料中残留的N,N-二甲基甲酰胺。

Objective：To develop a headspace GC method for the determination of residual N,N-dimethylformamide in cefalexin drug substance.Methods：A DB-624 column（30 m×0.32 mm×1.8 μm） was used,with nitrogen as carrier gas and FID as detector.The injecting port temperature was 200 ℃ and the detector temperature was 250 ℃,the oven temperature was a ramp program and the injection split ratio was 1：5.Results：A good linearity was obtained within the designed range of N,N-dimethylformamide（12.38-247.7 μg·mL-1,r=0.9998）.The limit of detection and limit of quantitation was 3.83 μg·mL-1（S/N=3：1） and 11.48 μg·mL-1（S/N=10：1）,respectively.All of the RSDs of precision,repeatability and roughness were less than 4.0%.The recoveries（n=3） of N,N-dimethylformamide（50%,100% and 120%） were between 85.7%-89.2% and the average recovery（n=9） was 86.9%.Conclusion：The method is simple,accurate and reproducible in detecting the residual N,N-dimethylformamide in cefalexin drug substance.