GC同时测定利伐沙班原料药中7种有机溶剂残留

Simultaneously Determination of Residual Organic Solvents in Rivaroxaban Drug Substance by GC

关键词:  毛细管气相色谱法  利伐沙班  乙酸  三乙胺  有机溶剂残留量

Key words:  GC  rivaroxaban  acetic acid  triethylamine  residual organic solvents

摘要:

目的 建立以毛细管气相色谱法测定利伐沙班原料药中乙醇、二氯甲烷、四氢呋喃、三乙胺、吡啶、乙酸、N，N-二甲基甲酰胺(DMF)7种有机溶剂残留量的方法。方法 采用Agilent DB-624(30.0 m×0.32 mm，1.8 μm)毛细管柱，载气为氮气，采用氢火焰离子化检测器(FID)，进样口温度为200 ℃，检测器温度为240 ℃，柱温采用程序升温，流速为2.0 mL·min^-1，进样量1 μL。结果 无水乙醇、二氯甲烷、四氢呋喃、三乙胺、吡啶、乙酸、DMF均能得到较好的分离，呈现良好的线性关系，平均回收率分别为102.4%，100.1%，96.5%，91.6%，103.6%，106.6%，102.5%，RSD均<5.0%。结论 本方法简便、快速、准确性好、灵敏度高，可用于利伐沙班原料药中残留溶剂的测定。

Abstract:

OBJECTIVE To establish a capillary GC method for the determination of residual organic solvents including alcohol, dichloromethane, tetrahydrofuran, triethylamine, pyridine, acetic acid, N, N-dimethylformamide (DMF) in rivaroxaban drug substance. METHODS This method utilized an Agilent DB-624 column(30 m×0.32 mm, 1.8 mm), N2 as carrier gas. FID was used as detector with the temperature of 240 ℃, and the inlet temperature was 200 ℃. This method used temperature program and the flow rate was 2.0 mL·min^-1. The injection volume was 1 μL. RESULTS The 7 residual organic solvents alcohol, dichloromethane, tetrahydrofuran, trimethylamine, pyridine, acetic acid, DMF were completely separated, the linear relationship was good, and the average recoveries were 102.4%, 100.1%, 96.5%, 91.6%, 103.6%, 106.6%, 102.5%, respectively, and the RSD were all <5.0%. CONCLUSION This method is simple, rapid, accurate and highly sensitive, which can be used for the determination of the residual organic solvents in rivaroxaban drug substance.