LC/MS法分析头孢替坦二钠原料中的杂质

本文应用LC/MS技术对头孢替坦二钠原料中的4种杂质进行了快速鉴定.根据头孢菌素的降解反应机制设计加速实验,确定头孢替坦的2个主要杂质为其碱水解产物;以1%冰醋酸溶液-乙腈-甲醇为流动相,经C18柱分离,通过电喷雾串联质谱负离子检测,获得各杂质的相对分子质量信息和碎片信息,并辅助UV特征对杂质结构进行了鉴定.在所建立的LC/MS条件下,头孢替坦及其杂质得到有效的分离,4个杂质经分析分别为5-巯基-1-甲基-四氮唑、头孢替坦内酯、头孢替坦脱羧物和头孢替坦异构体.本研究表明,利用LC/MS技术可推测头孢菌素类抗生素中杂质的结构,且本方法快速、灵敏、专属性高.

Characterization of related impurities in cefotetan bulk material by high-performance liquid chromatography-electrospray tandem mass spectrometry

LC/MS methods were developed for rapid identification of 4 impurities in cefotetan.Based on the degradation mechanism of Cephalosporins,stress tests were designed and performed,and it was found that two main impurites were base degradation products.Cefotetan disodium bulk material was separated on a C18 column,with 1% ice acetate solution-acetonitrile-methanol（80：10：10） as mobile phase.Under the negative ion mode,four impurities were separated from cefotetan components and identified on the basis of MS/MS spectra and the proposed general fragmentation pathway of cefotetan,as well as the UV spectra.Four impurites were characterized as 5-mercapto-1-methyl-tetrazole,cefotetan lactone,decarboxyl-cefotetan,and isomer cefotetan.Therefore,the method is rapid,sensitive and specific,and it is suitable for the identification of the impurities of cephalosporin.