In order to establish the quality control system of retigabine active substances, a head-space gas chromatographic method was established and validated for the determination of residual solvents of ethanol, hexane, tetrahydrofuran and triethylamine in retigabine active substances, by using FID as the detector and N, N-dimethylformamide as sample solvent. The detection of four residual solvents was performed on a DB-624 capillary column with vial equilibration temperature of 110 ℃ and equilibration time of 15 min. The limits of detection( LOD) for ethanol, hexane, tetrahydrofuran and triethylamine were 0. 007 5% , 0. 000 48% , 0. 002 4% and 0.01% , respectively. The relative standard deviations (RSDs) of peak areas were below 2. 1% . The average recoveries were in the range of 100% - 102% , and the correlation coefficients were above 0. 995. The result indicated that the method showed the advantages of high sensitivity, good accurancy and linearity. The established method was applied in the quality control of three batches of retigabine, and only ethanol and hexane were checked out with the highest residual level of 0. 149% and 0. 022% , respectively, which did not exceed the limited quantity.%建立了测定瑞替加滨原料药中残留溶剂乙醇、正己烷、四氢呋喃、三乙胺的顶空气相色谱方法.采用氢火焰离子化检测器,以N,N-二甲基甲酰胺为样品溶剂,通过对色谱条件优化,建立了以DB-624为分析柱、110℃为平衡温度、15 min为平衡时间的残留溶剂测定方法.经方法学验证,上述4种溶剂的方法检出限依次为0.007 5％、0.000 48％、0.002 4％、0.01％；峰面积的相对标准偏差均小于2.1％；平均回收率为100％～102％；4种溶剂的线性系数均大于0.995.结果表明,该方法的检测灵敏度高、精密度好、准确度高、线性关系良好,能够满足对瑞替加滨质量的控制要求.将该方法应用于3批瑞替加滨原料药的残留溶剂检测,均只检出乙醇和正己烷,且乙醇和正己烷的最高残留量分别为0.149％和0.022％,均未超出限量规定.
展开▼
