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建立并优化了一种二维柱切换、高效液相色谱-质谱联用(LC-MS/MS)系统,用于分析抗生素及其有关物质。在一维色谱中,采用两性离子交换-反相亲水性相互作用(ZIC-RP-HILIC)混合模式色谱柱对目标杂质进行分离,并采用液质联用技术(LC-MS/MS)进行检测。在二维色谱中,采用常规的反相LC色谱柱对供试品及其杂质进行分析。ZIC-RP-HILIC混合模式色谱系统的流动相为一种适用于LC-MS/MS的可挥发性缓冲盐,能够提高杂质的离子化效率,便于对目标杂质进行结构解析。直接采用ZIC-RP-HILIC-MS系统,对使用离子对反相色谱分离的抗生素杂质进行定性分析。ZIC-RP-HILIC混合模式色谱与反相LC色谱系统之间的正交性,进一步保证了杂质检测的全面性。此方法的优势体现在对青霉素V钾,苯唑青霉素钠、头孢曲松钠的杂质分析中。另外,该方法便于进行抗生素的杂质谱分析,并可用于其它药物的杂质分析。
A two-dimensional column-switching, high performance liquid chromatography-mass spectrometry (LC-MS / MS) system was established and optimized for the analysis of antibiotics and their related substances. In one-dimensional chromatography, the target impurities were separated by ZIC-RP-HILIC mixed mode column and analyzed by LC-MS / MS Detection. In 2D chromatography, the sample and its impurities were analyzed using a conventional reversed-phase LC column. The mobile phase of the ZIC-RP-HILIC mixed-mode chromatographic system is a volatile buffer salt for LC-MS / MS that improves the ionization efficiency of impurities for structural elucidation of target impurities. Directly using the ZIC-RP-HILIC-MS system, qualitative analysis of antibiotic impurities separated by ion-pair reversed-phase chromatography was performed. The orthogonality between ZIC-RP-HILIC mixed-mode and reversed-phase LC systems further ensures the comprehensiveness of impurity detection. The advantages of this method are reflected in the impurity analysis of penicillin V potassium, oxacillin sodium and ceftriaxone sodium. In addition, this method facilitates impurity profile analysis of antibiotics and can be used for impurity analysis of other drugs.