注射用头孢唑肟钠的聚合物杂质分析  

Analysis of polymer impurities in ceftizoxime sodium for injection

作　　者：李进[1] 姚尚辰[1] 宁保明[1] 胡昌勤[1] LI Jin;YAO Shang-chen;NING Bao-ming;HU Chang-qin(National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《中国新药杂志》2023年第1期72-79,共8页Chinese Journal of New Drugs

基　　金：中国食品药品检定研究院化药所重点实验室课题资助项目“抗生素药物杂质分析技术平台的建立与应用”(1030050090129)。

摘　　要：目的:建立注射用头孢唑肟钠聚合物杂质的分析方法。方法:采用pH 7.0磷酸盐溶液为溶剂,制备头孢唑肟钠降解溶液;采用高效分子排阻色谱法(HPSEC)和柱切换-液质联用法(CS-LC/MSn),对头孢唑肟钠降解溶液的弱保留值杂质进行分离和结构推定,评估HPSEC法分析聚合物杂质的专属性;采用Phenomenex Gemini C18色谱柱,以pH 7.0磷酸盐缓冲液-乙腈为流动相进行梯度洗脱,建立头孢唑肟钠聚合物的反相-高效液相色谱法(RP-HPLC),采用二维色谱法(2D-HPLC)和CS-LC/MSn法对其专属性进行分析,并测定了方法的定性限和定量限。结果:在头孢唑肟钠降解溶液中推定出头孢唑肟二聚体、二聚体异构体以及6种小分子杂质;HPSEC法分离头孢唑肟钠聚合物杂质时,小分子杂质与聚合物杂质共出峰,方法专属性与定量准确性差;RP-HPLC法分析头孢唑肟聚合物杂质时,能够检出头孢唑肟二聚体、二聚体异构体,专属性好。结论:HPSEC法不能对注射用头孢唑肟钠的聚合物杂质进行有效质量控制,建立的RP-HPLC法分析注射用头孢唑肟钠聚合物杂质的专属性良好,可将头孢唑肟钠降解溶液作为聚合物杂质系统适用性溶液。Objective:To establish a method for controlling polymer impurities in ceftizoxime sodium for injection.Methods:Ceftizoxime sodium was dissolved in phosphate buffer solution(pH 7.0)to prepare degradation solution.High performance size exclusion chromatography(HPSEC)and column switching-LC/MSn(CS-LC/MSn)were applied to separate and deduce the poor retention impurities in the degradation solution.The specificity of developed HPSEC method was evaluated.A RP-HPLC method for polymer analysis was established with a Phenomenex Gemini C18column,using phosphate buffer solution(pH 7.0)-acetonitrile as mobile phase under a gradient elution program.The specificity of RP-HPLC method was assessed by two-dimensional chromatography(2D-HPLC)and CS-LC/MSn,and LLOD and LLOQ were also tested.Results:ceftizoxime dimer and the dimer’s isomer were deduced in the degradation solution as well as 6 small molecular impurities.Polymer impurities were liable to co-elute with small molecular impurities by HPSEC method,which made a poor quantification accuracy and specificity.Ceftizoxime dimer and the dimer’s isomer were detected by RP-HPLC with a sufficient specificity.Conclusion:HPSEC method was not suitable for the quality control of polymer impurities in ceftizoxime sodium for injection,while the RP-HPLC method was specific,which can be applied for polymer impurities.Ceftizoxime degradation solution can be used to identify polymer peaks as the systematic suitability testing solution.

关 键 词：头孢唑肟钠 杂质 聚合物 柱切换-液质联用法 高效分子排阻色谱 二维色谱 Β-内酰胺抗生素 

分 类 号：R978.1[医药卫生—药品]