头孢唑林钠原料及制剂中的聚合物杂质研究

Research on polymer impurities in cefazolin sodium raw materials and products

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。

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.