气相色谱法测定替格瑞洛原料药中的残留溶剂

Determination of Residual Solvents in Bulk Drug of Ticagrelor by Headspace Gas Chromatography

建立替格瑞洛原料药中残留溶剂的气相色谱检测方法。采用DB-624毛细管色谱柱,初始柱温40℃,保持5 min,以30℃/min的速度升至200℃,保持4 min,载气为氮气,检测器为氢火焰离子化检测器(FID),顶空参数为80℃,平衡时间30 min。甲醇、乙酸乙酯、异辛烷、正庚烷、甲苯和N,N-二异丙基乙胺浓度分别在3. 003~450. 45,1. 002~750. 6,0. 1004~751. 2,0. 1004~751. 2,0. 891~133. 65,0. 5001~15. 15μg/m L范围内具有良好的线性;相关系数分别为0. 9984,0. 9988,1. 000,1. 000,0. 997 9,0. 999 4;平均回收率分别为97. 5%,97. 7%,98. 9%,98. 9%,95. 2%,97. 1%;检测限分别为0. 900 9,0. 300 6,0. 030 1,0. 030 1,0. 267 3,0. 150 0μg/m L;该方法验证3批替格瑞洛原料药中检测的残留溶剂均符合标准规定。该检测方法经方法学验证,适用于检测替格瑞洛原料药中甲醇、乙酸乙酯、异辛烷、正庚烷、甲苯和N,N-二异丙基乙胺的残留溶剂。

To establish a gas chromatography method for the determination of residual solvents in bulk drug of Ticagrelor,ADB-624 capillary column with nitrogen gas as carrier and flame ionization detector( FID) as detector were applied in this study. The column temperature was programmed to be: 40 °C for 5 minutes,then raised to 200 °C at a speed of 30 °C per minute and held for 4 minutes.Headspace parameters for 80 ° C and held for 30 minutes. The results showed that there was a very good linearity in the range of3. 003 ~ 450. 45 μg/m L for methanol( r = 0. 998 4),1. 002 ~ 750. 6 μg/m L for ethyl acetate( r = 0. 998 8),0. 100 4 ~ 751. 2 μg/m L for isooctane( r = 1. 000),0. 100 4 ~ 751. 2 μg/m L for normal heptane( r = 1. 000),0. 891 ~ 133. 65 μg/m L for methylbenzene( r =0. 997 9),0. 500 1 ~ 15. 15 μg/m L for N,N-diisopropyl ethylamine( R = 0. 999 4). The average recoveries for methanol、ethyl acetate、isooctane、normal heptane、methylbenzene and N,N-diisopropyl ethylamine were 97. 5%,97. 7%,98. 9%,98. 9%,95. 2%,97. 1% respectively. The LOQ were 0. 900 9,0. 300 6,0. 030 1,0. 030 1,0. 267 3,0. 150 0 μg/m L,respectively. The results of residual solvents in three batches of Ticagrelor were all agreed with the regulation. The method was proved by methodology validation to be suitable for the detection of methanol、ethyl acetate,isooctane,normal heptane,methylbenzene and N,N-diisopropyl ethylamine in bulk drug of Ticagrelor.