盐酸头孢他美酯中有关物质的结构鉴定

Structure elucidation of impurities in cefetamet pivoxil hydrochloride

目的:采用核磁共振法鉴定盐酸头孢他美酯原料药中3个有关物质的结构。方法:首先采用制备色谱分离出盐酸头孢他美酯原料药中的3个杂质,然后采用LC-Q-TOF-MS、LC-Q-TRAP-MS/MS/MS、 ~1H-NMR、 ^(13)C-NMR、DEPT、 ~1H-~1H COSY、HSQC、HMBC、 IR和UV数据对杂质进行结构鉴定。结果:通过光谱数据分析,鉴定出盐酸头孢他美酯原料药中3个杂质的结构,并进行归属。3个杂质分别为新戊酰头孢他美酯(杂质Ⅰ)、头孢他美酯二聚物(杂质Ⅱ)、8-(1-硫-2-羰基-3-甲氧基-1-异丁烷)-苯并噻唑(杂质Ⅲ),杂质类型主要为聚合以及头孢他美酯合成副产物。结论:该研究鉴定了头孢他美酯原料药中的3个杂质,对头孢他美酯的质量控制具有指导意义。

Objective:To identify and characterize the structures of three impurities in cefetamet pivoxil hydrochloride drug substances by NMR.Methods:Three impurities in cefetamet pivoxil hydrochloride drug substances were obtained by preparative HPLC,and the structures were elucidated and confirmed by spectral data(LC-Q-TOF-MS,LC-Q-TRAP-MS/MS/MS、1H-NMR、13C-NMR、DEPT、1H-1H COSY ,HSQC,HMBC,IR and UV)comprehensively.Results:Based on the spectral data,the structures of three impurities were characterized as pivalyl cefetamet pivoxil(impurity Ⅰ),dimer of cefetamet pivoxil(impurity Ⅱ)and 8-(1-sulfur-2-carbonyl-3-methoxyl-1-isobutane)-benzothiazole(impurity Ⅲ).The impurities include polymerization and synthesis by-product of cefetamet pivoxil.Conclusion:This established method is suitable for the identification of related substances and provides a tool for the quality control ofcefetamet pivoxil hydrochloride.