气相色谱法测定替格瑞洛原料药中6种残留溶剂  

Determination of six residual solvents in ticagrelor raw material by capillary gas chromatography

作　　者：杜娟[1] 魏双艳[1] 徐晓阳[1] 阴兆静 张玮杰 李惠举[1] 徐霞[1] 

机构地区：[1]郑州大学药学院药物分析教研室,郑州450001

出　　处：《郑州大学学报（医学版）》2017年第5期621-624,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：河南省科技厅基础与前沿技术研究计划项目142300410085;郑州市国际科技合作与交流项目153PGJHZ204

摘　　要：目的:建立替格瑞洛原料药中6种残留溶剂的测定方法。方法:采用气相色谱法检测替格瑞洛原料药中甲醇、乙醇、乙腈、乙酸乙酯、异辛烷、乙酸。色谱条件为DB-624(30 m×0.320 mm×1.8 mm)毛细管柱;载气采用高纯氮气,流速为1 m L/min;检测器为氢火焰离子化检测器,检测器温度为250℃(空气流速),进样口温度为200℃;程序升温,分流比20∶1。结果:6种有机溶剂在各自的检测质量范围内线性关系良好(r=0.998 31~0.999 99),平均回收率为91.49%~100.48%(RSD=2.85%~7.17%,n=9);甲醇、乙醇、乙腈、乙酸乙酯、异辛烷、乙酸的定量限分别为7.92、7.89、6.29、0.90、0.23、4.20 mg/L,检测限分别为1.98、0.99、0.79、0.22、0.08、1.05 mg/L。用该方法测定3批次替格瑞洛原料药,只有乙酸乙酯和异辛烷被检出但均符合标准,其他残留溶剂未检测到。结论:该方法操作简便、稳定、重复性好,可用于替格瑞洛原料药中上述6种残留溶剂的测定。Aim： To develop a method for the content determination of residual solvents in ticagrelor raw material including methanol,ethanol,acetonitrile,ethyl acetate,isooctane,and acetic acid. Methods： Capillary gas chromatography was adopted. The determination was performed on DB-624（ 30 m × 0. 320 mm × 1. 8 mm） capillary column,a flame ionization detector（ FID） and the external standard method were used for the separation and quantitative analysis. The condition was that the injector temperature was 200 ℃,the FID temperature was 250 ℃ and the residual organic solvents were determined by the split injection mode. Results： The good linear range of the 6 kinds of residual solvents had been obtained（ r = 0. 998 31-0. 999 99） with average recoveries of 91. 49%-100. 48%（ RSD = 2. 85%-7. 17%,n = 9）. The limits of quantification of the 6 kinds of residual solvents were 7. 92,7. 89,6. 29,0. 90,0. 23 and 4. 20 mg/L; the detection limits were 1. 98,0. 99,0. 79,0. 22,0. 08 and 1. 05 mg/L. The proposed method was successfully applied to analyze the residual organic solvent in the real sample of ticagrelor raw material,and the results showed that only ethyl acetate and isooctane were detected in the samples. Conclusion： The method is rapid,stable and repeatable for the content determination of the6 kinds of residual solvents in ticagrelor raw material.

关 键 词：替格瑞洛原料药 毛细管气相色谱法 残留溶剂 

分 类 号：R917[医药卫生—药物分析学]