液相色谱-四极杆飞行时间质谱法分析头孢拉定中的主要杂质

目的: 采用液相色谱-四极杆飞行时间串联质谱法(HPLC-Q-TOF-MS)分析头孢拉定中主要杂质并对其结构进行鉴定。方法: 色谱柱为Kromasil 100-5C₁₈(250 mm×4.6 mm,5 μm),流动相为甲醇-10 mmol·L^-1醋酸铵溶液(30:70);离子源:ESI离子源;扫描模式:正离子扫描。结果: 本方法通过四极杆-飞行时间二级质谱图特征碎片的分析确定了头孢拉定中1.32%的未知杂质为双氢头孢拉定,同时推测该杂质可能是中间体双氢苯甘氨酸中的杂质(四氢苯甘氨酸)参与合成引进的。结论: 本方法鉴定了头孢拉定中的1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 HPLC-Q-TOF-MS method for the identification of major impurities in cefradine. Methods: The HPLC was performed on a Kromasil 100-5C₁₈ column (250 mm×4.6 mm, 5 μm) with methanol-10 mmol·L^-1 a mmonium acetate (30:70) as mobile phase.Data was collected under positive ion modes with ESI as ion resource. Results: The method identified an impurity with the content of 1.32% as dihydrocefradine based on analysis the feature fragmentation from Q-TOF.It was speculated that the impurity was introduced by intermediate dihydrophenylglycine impurities involved in the synthesis process. Conclusion: The method identified an unknown impurity in cefradine, and thus provide reference to its quality control and process optimization.