顶空气相色谱法测定头孢唑兰原料药中的5种有机溶剂残留量

Determination of 5 kinds of organic solvent residues in cefozopran by headspace gas chromatography

目的建立测定头孢唑兰原料药中甲醇、乙醇、丙酮、二氯甲烷和乙酸乙酯5种有机溶剂残留量的方法。方法采用顶空气相色谱法。检测器为氢火焰离子化检测器(FID);色谱柱为Agilent DB-624毛细管柱(30m×0.32mm,1.8μm);溶剂为二甲基亚砜;进样口温度为220℃;检测器温度为250℃;分流比为20∶1;用程序升温;氮气为载气;氢气和空气为燃气;顶空平衡温度90℃;平衡时间30min;进样体积1mL。结果 5种有机溶剂在建立的色谱条件下均能完全分离,分离度均大于1.5,理论塔板数均大于10 000;在考察质量浓度范围内线性关系良好(甲醇、乙醇、丙酮、二氯甲烷和乙酸乙酯的r值分别为0.998 3,0.997 7,0.998 5,0.995 5和0.997 7);定量限分别为29.850,30.225,3.960,15.100和3.675μg·mL^(-1);检测限分别为7.460,7.560,1.190,4.530和1.100μg·mL^(-1);重复性RSD值均小于2.5%(n=6);平均回收率范围为98.00%～101.44%;混合对照品溶液在10h内稳定性良好。结论该方法操作简便、灵敏、结果准确、可靠,可用于头孢唑兰原料药中有机溶剂残留量的控制。

Objective To establish a headspace gas chromatography method for the determination of methanol,ethanol,acetone,methylene chloride and ethyl acetate residual solvents in cefozopran. Methods The experiment was carried out by headspace gas chromatography with a hydrogen flame ionization detector （FID） and an Agilent DB-624 capillary column （30 m×0.32 mm,1.8 μm）.The sample was dissolved in DMSO solvent.The temperature of Inlet was 220 ℃ and the temperature of detector was 250 ℃.The split ratio was set to 20∶1.Program temperature was used in the whole process,and N 2 was used as carrier gas,H 2 and air were used as burn gas.The headspace balance temperature was 90 ℃,and the balance time was 30 min.In such conditions,the sample was injected 1 mL each time. Results 5 kinds of organic solvents were completely separated under the established chromatographic conditions, R 〉1.5, N 〉10 000;the linear relationships were good in the mass concentration ranges （methanol r = 0.998 3, ethanol r = 0.997 7, acetone r = 0.998 5, dichloromethane r = 0.995 5, ethyl acetate r =0.997 7）;the limit of quantification was 29.850,30.225,3.960,15.100 and 3.675 μg·mL -1 ,respectively;the limit of detection were 7.460,7.560,1.190,4.530 and 1.100 μg·mL -1 ,respectively.The average recovery rates were between 98.44%-101.44%.The mixed reference substances kept stable within 10 h. Conclusion The method is simple,sensitive,accurate and reliable,and can be used for the control of residual solvents in cefozopran.