药学学报, 2021, 56(6): 1677-1682
引用本文:
张夏, 李进, 王晨, 刘颖, 姚尚辰, 尹利辉, 许明哲*, 胡昌勤*. 头孢唑林钠原料及制剂中的聚合物杂质研究[J]. 药学学报, 2021, 56(6): 1677-1682.
ZHANG Xia, LI Jin, WANG Chen, LIU Ying, YAO Shang-chen, YIN Li-hui, XU Ming-zhe*, HU Chang-qin*. Research on polymer impurities in cefazolin sodium raw materials and products[J]. Acta Pharmaceutica Sinica, 2021, 56(6): 1677-1682.

头孢唑林钠原料及制剂中的聚合物杂质研究
张夏, 李进, 王晨, 刘颖, 姚尚辰, 尹利辉, 许明哲*, 胡昌勤*
中国食品药品检定研究院, 国家药品监督管理局重点实验室化学药品质量研究与评价重点实验室, 北京 102629
摘要:
聚合物杂质研究一直是头孢菌素类抗生素质量控制中的重要内容。7位侧链中不含活性基团氨基的头孢菌素的聚合物研究还未有报道,因此本研究以临床上广泛采用的头孢唑林钠为例,采用柱切换液相色谱-高分辨质谱联用法分析头孢唑林钠原料及制剂中的聚合物,结果检测到2个聚合物杂质峰,并对聚合物的可能结构进行了推测。通过二维液相色谱法,将葡聚糖凝胶色谱法和高效凝胶色谱法中的色谱峰切入到头孢唑林钠药典方法的有关物质方法(反相高效液相色谱法)中,证明反相高效液相色谱法比葡聚糖凝胶色谱法和高效凝胶色谱法更适于聚合物检测。最终采用药典有关物质方法建立了头孢唑林钠原料和制剂的聚合物检测方法,并进行了方法学验证。
关键词:    聚合物杂质      头孢唑林钠      柱切换液相色谱-高分辨质谱联用      二维液相色谱      葡聚糖凝胶色谱法      高效凝胶色谱法     
Research on polymer impurities in cefazolin sodium raw materials and products
ZHANG Xia, LI Jin, WANG Chen, LIU Ying, YAO Shang-chen, YIN Li-hui, XU Ming-zhe*, HU Chang-qin*
Key Laboratory of State Drug Administration-Key Laboratory of Research and Evaluation of Chemical Drug Quality, National Institutes for Food and Drug Control, Beijing 102629, China
Abstract:
Research on polymer impurities has always been important in the quality control of cephalosporins. Research on polymers in cephalosporins that lack active amino groups on the C-7 side chain has not been reported. Therefore, our study used cefazolin sodium, which is widely used in the clinic, as an example. The polymer in cefazolin sodium and its product "cefazolin sodium pentahydrate for injection" was analyzed by column switching liquid chromatography-high resolution mass spectrometry. Two polymer impurity peaks were detected and the possible structures of these polymers were suggested. Through two-dimensional liquid chromatography, the chromatographic peaks following Sephadex gel chromatography and high-performance gel chromatography were compared to those obtained by reverse high-performance liquid chromatography (HPLC) for cefazolin sodium as reported in the Chinese Pharmacopoeia. The HPLC method proves more suitable for polymer detection than Sephadex gel chromatography and high-performance gel chromatography. The method of polymer detection for cefazolin sodium was established using the method of related substances HPLC as described in the Chinese Pharmacopoeia.
Key words:    polymer impurity    cefazolin sodium    column switching liquid chromatography-high resolution mass spectrometry    two-dimensional liquid chromatography    sephadex gel chromatography    high-performance gel chromatography   
收稿日期: 2020-12-10
DOI: 10.16438/j.0513-4870.2020-1601
基金项目: 化学药品质量研究与评价重点实验室项目(1030050090129).
通讯作者: 许明哲,Tel:86-10-53852506,E-mail:xumingzhe@nifdc.org.cn;胡昌勤,Tel:86-10-53851531,E-mail:hucq@nifdc.org.cn
Email: xumingzhe@nifdc.org.cn;hucq@nifdc.org.cn
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