LC-MS分离鉴定头孢地嗪热降解的异构体杂质

LC-MS method for the isolation and identification of isomeric impurities by thermal degradation in cefodizime

目的:建立应用高效液相色谱-串联质谱技术快速鉴定头孢地嗪中异构体杂质的方法。方法:以5 mmol.L-1醋酸铵溶液-乙腈为流动相,经C18柱(200 mm×4.6 mm,5μm)分离,通过串联ESI质谱在线检测,获得相关的色谱和质谱信息。结果:在所建立的条件下,头孢地嗪及其异构体杂质获得有效分离,头孢地嗪、反式异构体及Δ3异构体的保留时间分别为11.38,14.26,10.95 min,通过质谱中特征碎片离子的差异可区分反式异构体及Δ3异构体。结论:本法可快速、准确地分离鉴定头孢地嗪中的反式和Δ3异构体杂质,进而可以对药品质量进行质量控制。

Objective：To establish a sensitive and specific LC-MS method for the determination of isomeric impurities in cefodizime.Methods：The HPLC separation experiments were performed on a reversed phase C18 column（200 mm×4.6 mm,5 μm）,with 5 mmol·L-1 ammonium acetate-acetonitrile as mobile phase.The analytes were determined by ESI-MS in negative mode.The chromatograms and mass spectra of cefodizime and its isomeric impurities were obtained by LC-MS.Results：The method can be used for the separation and identification of cefodizime and its anti-form,Δ3-cephem form,of which the retention times were 11.38,14.26,10.95 min,respectively.Based on the MS spectra of their molecular ion,the different fragmentation pathways of cefodizime and its isomeric impurities were compared and proposed.Conclusion：The method is rapid,sensitive and specific.It can be used for the identification of the isomeric impurities in cefodizime.