第 52 卷第 5 期 Vol. 52 No. 5 2022 年 10 月 Oct 2022

所属栏目：分析与测试 注射用头孢唑林钠中一种头孢唑林聚合物分析

于晓娜，表亚囡，刘 莹，时佳静，谷艺凡，任毅然，李 敏，杨梦德，张 民* （华北制药河北华民药业有限责任公司 抗生素酶催化与结晶技术国家地方联合工程实验室 河北省头孢类药物制备技术创新中心，河北 石家庄 052165）

摘　要：头孢类抗生素聚合物多为总聚物的控制，为更好进行聚合物单个控制，建立RPHPLC法并采用柱切换-LC/MSn对聚合物杂质进行定性研究。结果显示该方法可有效检出聚合物A且专属性良好，对聚合物A进行结构确证并推测其产生机理，同时对该方法进行全面的方法学验证。各个破坏条件下聚合物A与相邻杂质分离度大于1.5；检测限及定量限浓度相当于供试品浓度的0.01%及0.02%；聚合物A在定量限至4倍限度浓度范围内与峰面积的线性关系良好，相关系数大于0.99；样品中聚合物A的加标回收率在93.44%~100.96%范围内；重复性、中间精密度中聚合物A的含量极差均为0.00%；聚合物A在常温下稳定性较差，在冷藏条件下24 h内较稳定；在波长变化±5 nm、柱温变化±5 ℃，流速变化±0.1 mL/min、pH在6.7~6.8范围内及不同色谱柱条件下，聚合物A专属性良好，含量与正常条件比较无明显差异。该方法专属性良好，准确度及重复性较高，可以用于检测注射用头孢唑林钠中的单个的头孢唑林聚合物。

关键词：高效凝胶色谱法；头孢唑林钠；聚合物杂质；结构确证；方法学验证

中图分类号：R927.1　　文献标识码：A　　文章编号：1009-9212（2022）05-0091-06

Analysis of Polymeric Impurity in Cefazolin Sodium for Injection

YU Xiao-na, BIAO Ya-nan, LIU Ying, SHI Jia-jing, GU Yi-fan, REN YI-ran, LI Min, YANG Meng-de, ZHANG Min* (Huabei Pharmaceutical Hebei Huamin Pharmaceutical Co., Ltd., National and local Joint Engneering Laboratory of Antibiotic Enzyme Catalysis and Crystallization Technology, Hebei Province Cephalosporide Medicine Preparation Technology Innovation Center, Shijiazhuang 052165, China)

Abstract：Cephalosporin antibiotics are mostly controlled by total polymers. In order to better control the single polymer. The method of RPHPLC was established column switching-LC/MSn was used to qualitatively polymeric impurities. The results showed that this method could effectively detect polymer A with good specificity. The structure of polymer A was confirmed and the mechanism of its generation was speculated. Meanwhile, the method was comprehensively validated. The separation degree of polymer A and its adjacent impurities was greater than 1.5 under each failure condition. Limit of detection and limit of quantitation concentration were equivalent to 0.01% and 0.02% of the concentration of the tested substance; The linear relationship between polymer A and peak area was good in the concentration range from the limit of quantification to the limit of four times, and the correlation coefficient was greater than 0.99. The recoveries of polymer A ranged from 93.44% to 100.96%. The content range of polymer A in repeatability and intermediate precision was 0.00%. The stability of polymer A was poor at room temperature, but stable within 24 h under cold storage. Under the following conditions: wavelength change was ±5 nm; column temperature change was ±5 ℃; flow rate change was ±0.1 mL/min; pH value in the range of 6.7~6.8 and different chromatographic column conditions, polymer A had good specificity and no significant difference in content compared with normal conditions. This method had good specificity, accuracy and repeatability, and could be used for the determination of single polymer in cefazolin sodium for injection.

Key words：high performance gel chromatography; cefazolin sodium; polymeric impurities; structure confirmation; method validation

作者简介：于晓娜（1987—），女，河北石家庄人，工程师，研究方向：药品质量研究（E-mail：yuxiaona1427@126.com）。

联 系 人：张 民，高级工程师，研究方向：药品工程研究（E-mail：3199365250@qq.com）。

收稿日期：2022-06-14