顶空气相色谱法测定依帕司他有机溶剂残留量

Determination of Residual Organic Solvents in Epalrestat by Headspace GC

关键词:  依帕司他  残留溶剂  顶空气相色谱法

Key words:  epalrestat  residual solvent  headspace GC

摘要:

目的 建立测定依帕司他原料药中残留有机溶剂甲醇、乙醇、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、甲苯的检测方法，为建立质量标准提供依据。方法 采用DB-624毛细管柱（30 m×0.53 mm，3.0 μm），氢火焰离子化检测器（FID），进样口温度210℃，检测器温度250℃，程序升温，流速3.0 mL·min^-1，分流比10：1，顶空平衡温度85℃，平衡时间30 min，按内标法（内标物叔戊醇）测定各残留溶剂的含量。结果 药物中7种残留溶剂的精密度RSD均<5%，在各自的浓度范围内具有良好的线性关系，相关系数均>0.999，平均回收率为90.0%~100.0%。结论 本方法专属性好，灵敏度高，操作简单，测定结果准确，适用于依帕司他原料药7种残留溶剂的同时测定。

Abstract:

OBJECTIVE To establish a method for the determination of residual solvents (methanol, ethanol, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, toluene) in epalrestat for controlling the quality of epalrestat. METHODS The solvents were separated on DB-624 capillary column(30 m×0.53 mm, 3.0 μm) with programming temperature, and detected using hydrogen flame ionization detector(FID). The headspace and other chromatographic conditions were as follows:250℃ of detector temperature, 3.0 mL·min^-1 of flow rate, 10:1 of split ratio, 210℃ of inlet temperature, 85℃ of equilibrium temperature and 30 min of equilibrium time. The contents of residual solvents were determined according to the internal standard method(internal standard tert-amyl alcohol). RESULTS There were good linear relationship in the concentration ranges with correlation coefficient above 0.999, respectively. The precisions (RSD values) were less than 5% in all seven kinds of residual solvents, and the average recoveries were within 90.0%-100.0%. CONCLUSION This method had good specificity, high sensitivity, simple operation and accurate results. It was suitable for the determination of above 7 kinds of residual solvents in Epalrestat API at same time.