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注射用头孢他啶有关物质的色谱-质谱结构鉴定
注射用头孢他啶有关物质的色谱-质谱结构鉴定
王双双,宋 凡,杭太俊,宋 敏

中国药科大学药物分析教研室,药物质量控制与药物警戒教育部重点实验室,南京 210009
Identification of the related substances in ceftazidime for injection by LC-MS techniques
(Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education)

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起始页:102

摘要:[摘要] 目的:采用色谱-质谱联用技术鉴定注射用头孢他啶的有关物质,为其质量研究和控制提供参考依据。方法:采用Thermo Syncronis C18(250 mm×4.6 mm,5 μm)色谱柱,以乙腈-0.1%乙酸铵缓冲液为流动相梯度洗脱,对注射用头孢他啶有关物质进行分离;采用电喷雾正离子化-飞行时间质谱法(ESI-TOF/MS)测定各有关物质的准确质量和元素组成,三重四极质谱(ESI-MS/MS)测定子离子特征,质谱解析鉴定有关物质的结构。结果:在所建立的条件下,头孢他啶及其有关物质分离良好,检测并鉴定出9个主要有关物质,其中4个为欧洲药典规定杂质,5个为新鉴定的未知杂质。结论:色谱-质谱联用技术能有效地分离鉴定头孢他啶中的有关物质,为其稳定性研究和质量控制提供技术支持。

关键词:[关键词] 头孢他啶;有关物质;降解产物;结构鉴定;色谱-质谱联用

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Abstract:[Abstract] Objective: To identify the related substances in ceftazidime for injection by LC-MS techniques for its stability study and quality control. Methods: A Thermo Syncronis C18 (250 mm×4.6 mm, 5 μm) column was used for separation of the related substances with a mixture of acetonitrile and ammonium acetate buffer as the mobile phase in gradient elution. Electrospray positive ionization high resolution TOF/MS was used for determining the accurate mass and elemental composition of parent ions of the related substances. Triple quadrupole tandem mass was employed for determining the product mass spectra. The structures of the related substances were then figured out through the elucidation of the fragment ions. Results: Ceftazidime and the related substances were separated under the established HPLC conditions. Nine major related substances in ceftazidime were detected and speculated by the hyphenated techniques. The four major impurities were recorded in British Pharmacopoeia, while another five were not reported before. Conclusion: The established LC-MS method is effective for separation and identification of the related substances in ceftazidime, and the results are useful for the stability study and quality control of ceftazidime.

Key words:[Key words] ceftazidime; related substances; degradation products; structure identification; LC-MS

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