液质联用法分析头孢呋辛酯原料药中的未知杂质

目的：采用液相色谱-飞行时间质谱法分析头孢呋辛酯中主要未知杂质并对其结构进行鉴定。 方法：色谱柱为ACQUITY UPLC^® BEH C₁₈（2.1 mm×50 mm，1.7 μm），流动相为甲醇-0.01 mol·L^-1醋酸铵溶液（30：70）；分别以1.0 mol·L^-1盐酸、0.05 mol·L^-1氢氧化钠溶液、60℃水浴、1%过氧化氢溶液破坏30 min，得到酸、碱、热、氧化破坏产物。质谱离子源为ESI离子源，扫描模式为正离子扫描，电离电压为2.5 kV，锥孔电压25 V，质量扫描范围为m/z 200~1000。 结果：本方法通过飞行时间质谱特征碎片的分析及合成验证，推测头孢呋辛酯中有关物质为头孢呋辛酸、头孢呋辛酸甲酯和头孢呋辛酯亚砜。 结论：本方法鉴定了头孢呋辛酯原料药中的多个未知杂质，进而可以对药品杂质控制和工艺优化提供参数。

Objective: To establish an UPLC-MS method for the analysis and identification of unknown impurities in cefuroxime axetil. Methods: The UPLC was performed on an ACQUITY UPLC^®BEH C₁₈(2.1 mm×50 mm,1.7 μm)with methanol-0.01 mol·L^-1 ammonium acetate (30: 70) as mobile phase.After treatment with 1.0 mol·L^-1 hydrochloric acid,0.05 mol·L^-1 sodium hydroxide solution,60℃ heating in water bath and 1% hydrogen peroxide solution for 30 minutes,acid,alkali,heat and oxidative damage products were obtained.Data was collected in positive ion modes with ESI as ion resource.The spurse voltage was kept at 2.5 kV and the cone voltage was 25 V with the mass range of m/z 200-1000. Results: The method identified lots of unknown impurities based on the analysis of the feature fragmentation from MS and verification of synthetic products,such as cefuroxime acid,methyl cefuroxime and cefuroxime axetil sulfoxide. Conclusion: The method identified a number of unknown impurities in cefuroxime axetil,and thus provided reference for its quality control and process optimization.