顶空-气相色谱法测定依度沙班原料药中8种有机溶剂

Determination of 8 kinds of residual organic solvents in edoxaban by headspace gas chromatography

建立顶空-气相色谱法同时测定依度沙班原料药中甲醇、乙醇、乙腈、二氯甲烷、正己烷、三氯甲烷、四氢呋喃和乙酸乙酯8种有机溶剂的方法。选用DB-624型毛细管柱为色谱柱,程序升温,进样口温度为150℃,FID检测器温度为250℃,载气为高纯氮气,载气流速为2.0 mL/min,分流比为10∶1,顶空加热温度为80℃,顶空进样量为1 mL,平衡时间为30 min。8种有机溶剂在各自的质量浓度范围内与色谱峰面积线性关系良好,相关系数均不小于0.9996,方法检出限均不大于15μg/mL。测定结果的相对标准偏差不大于3.4%。样品加标回收率为92.41%~101.60%。该方法操作简单,灵敏度高,结果准确,可用于依度沙班原料药中有机溶剂的测定。

The method was established for the determination of 8 kinds of organic solvents in edoxaban as methanol,ethanol,acetonitrile,dichloromethane,n-hexane,chloroform,tetrahydrofuran and ethyl acetate.Headspace gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The inlet temperature was 150℃,and flame ionization detector was used with temperature of 250℃.High purity nitrogen was used as carrier gas with flow rate of 2.0 mL/min.The split ratio was 10∶1.Headspace heating temperature was 80℃,headspace sample size was 1 mL,and equilibration time was 30 min.The mass concentration of 8 kinds of organic solvent had a good linear relationship with the chromatographic peak area in their respective ranges,the correlation coefficients were not less than 0.9996,and the detection limits of the method were not more than 15μg/mL.The relative standard deviation of the measurement results were not more than 3.4%.The average recoveries of the standard addtion were 92.41%-101.60%.The method was simple,rapid,sensitive,with good specificity,and it can be used for the determination of organic solvent in edoxaban.