盐酸头孢甲肟原料及制剂的聚合物杂质分析  

Analysis of polymer impurities in cefmenoxime hydrochloride raw material and preparations

作　　者：李进[1] 姚尚辰[1] 尹利辉[1] 许明哲[1] 胡昌勤[1] LI Jin;YAO Shang-chen;YIN Li-hui;XU Ming-zhe;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：《药物分析杂志》2021年第1期169-179,共11页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立盐酸头孢甲肟原料及制剂聚合物杂质的分析方法。方法:采用高浓度溶液降解法制备盐酸头孢甲肟降解溶液;采用高效凝胶色谱法(TSK G2000 SWxl)和柱切换-LC/MSn法对盐酸头孢甲肟降解溶液的聚合物杂质进行分离和结构鉴定,并评估高效凝胶色谱法分离聚合物杂质的专属性;采用Kromasil100-5 C_(18)型色谱柱,以水-乙腈-冰醋酸为流动相进行梯度洗脱,建立盐酸头孢甲肟聚合物的RP-HPLC分析方法,采用二维色谱法和柱切换-LC/MSn法对该方法的专属性进行分析,并对实际供试品进行分析。结果:在盐酸头孢甲肟降解物中鉴定出盐酸头孢甲肟脱3位侧链二聚体及二聚体开环水解物,未发现三聚体及四聚体杂质;高效凝胶色谱法分离盐酸头孢甲肟聚合物杂质时,易受到小分子杂质的干扰,方法专属性与定量准确性差;RP-HPLC法分析盐酸头孢甲肟聚合物杂质时,能够检出盐酸头孢甲肟二聚体及其异构体,专属性良好。结论:高效凝胶色谱法不能对盐酸头孢甲肟的聚合物杂质进行有效质控,建立的反相色谱法分析盐酸头孢甲肟聚合物杂质的专属性良好,可将盐酸头孢甲肟降解溶液可作为聚合物杂质系统适用性溶液。Objective:To establish a method for determination of polymer impurities in cefmenoxime hydrochloride raw materials and preparations.Methods:A high concentration solution was degradated to prepare degradation solution;High performance size exclusion chromatography method(HPSEC,with TSK-gel G2000 SWxl column,)and column switching-LC/MSn method were applied to separate and identify the polymer impurities in cefmenoxime hydrochloride degradation solution and evaluate the specificity of HPSEC method;a new RP-HPLC method for polymer analysis was established with an Kromasil 100-5,C18 column,using a mobile phase gradient elution by water-acetonitrile-glacial acetic acid.The specificity of RP-HPLC method was assessed by dimensional chromatography method and column switching-LC/MSn method,and the polymers in samples were analyzed by RP-HPLC method.Results:A series of polymer impurities in cefmenoxime hydrochloride degradation solution were identified including cefmenoxime dimmers and isomers,but no trimers or tetramers were detected.Polymer impurities were liable to co-elute with small molecular impurities by HPSEC method,leading to a poor quantification accuracy and specificity.Cefmenoxime dimer and isomer were detected by RP-HPLC method with a satisfied specificity.Conclusion:HPSEC method is not suitable for the quality control of polymer impurities in cefmenoxime hydrochloride raw materials or productions,while the new established RP-HPLC method is specific,which can effectively control the polymer impurities.Cefmenoxime dimer degradation solution can be used to identify polymer peaks as the system suitability solution.

关 键 词：盐酸头孢甲肟 半合成头孢菌素 Β-内酰胺抗生素 聚合物 杂质 柱切换-液质联用法 高效凝胶色谱 二维色谱 

分 类 号：R917[医药卫生—药物分析学]