顶空气相色谱法测定N-芴甲氧羰基-O-叔丁基-L-_苏氨酸中的残留溶剂

目的：建立顶空气相色谱法测定N-芴甲氧羰基-O-叔丁基-L-苏氨酸中的正己烷、丙酮、四氢呋喃、乙酸乙酯、甲醇、二氯甲烷、乙醇、乙腈和二氧六环共9种残留溶剂。 方法：采用DB-WAX毛细管色谱柱(30m×0.32mm，0.50μm)，顶空进样;进样口温度为200 ℃。以FID为检测器，检测器温度为250 ℃，程序升温，初始温度40 ℃维持6 min，以5 ℃·min^-1的升温速率升至220 ℃，维持10 min。顶空瓶平衡温度为85 ℃，平衡时间为30 min，载气为高纯氮气，进样体积1mL。 结果：各溶剂线性良好，相关系数r均≥0.9973;9种溶剂的检测限范围为0.035~2.366 μg;平均回收率为94.1%~107.7%。 结论：经方法学验证，所建立的方法准确、简便、重复性好，可用于测定N-芴甲氧羰基-O-叔丁基-L-苏氨酸中的残留溶剂，有效地控制药品质量。

Objective:To establish a headspace capillary GC method for the determination of residual solvent(n-hexane,acetone,tetrahydrofuran,acetic ether,methanol,dichloromethane,ethanol,acetonitrile,dioxane)in N-carbonyl oxygen fluorene armor-O-tert-butyl-L-threonine. Methods: The GC method was conducted on a DB-WAX capillary column(30 m×0.32 mm,0.50 μm)with headspace injection.The injector was set at 200 ℃.The temperature of FID was set at 250 ℃.The temperature program consisted of an initial temperature of 40 ℃ held for 6 min,rising to 220 ℃ at a rate of 5 ℃·min^-1and held for 10 min.The equilibrium temperature of the headspace bottles was 85 ℃;the equilibrium time was 30 min,the carrier gas was high purity nitrogen.The injection volume was 1 mL. Results: Good linear relationships of 9 solvents were obtained.And all correlation coefficients were no less than 0.9973;the limits of detection were in the range of 0.035-2.366 μg;the average recoveries were in the range of 94.1%-107.7%. Conclusion :The established method is accurate,simple and reproducible by methodology validation.It is suitable to determinate residual solvent in N-carbonyl oxygen fluorene armor-O-tert-butyl-L-threonine and can be effectively used for quality control of the drug.