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 C18 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 G2000SWxl 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.
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