头孢克肟原料及制剂的聚合物杂质分析

Analysis of polymer impurities in cefixime raw materials and preparations

建立头孢克肟原料及制剂中聚合物杂质的分析方法。通过强制聚合法制备富含聚合物杂质的头孢克肟降解溶液;然后采用高效凝胶色谱法和柱切换-LC-MSn法对降解溶液中的聚合物杂质进行分离和结构鉴定;采用Phenomenex Gemini-C18型色谱柱,以0.5%甲酸水溶液-0.5%甲酸乙腈溶液为流动相,进行梯度洗脱,建立RP-HPLC法分析头孢克肟聚合物,并进行方法学验证。结果表明,高效凝胶排阻色谱法分离头孢克肟聚合物杂质时,部分小分子杂质与聚合物共出峰,方法专属性差、定量准确性差;RP-HPLC法分析头孢克肟聚合物杂质时,能够检出2种头孢克肟二聚体、脱水二聚体等3种聚合物杂质峰,专属性好、灵敏度高、方法耐用性好,因此RP-HPLC法可用于头孢克肟的聚合物杂质的质量控制。头孢克肟降解溶液可作为分析头孢克肟聚合物的系统适用性溶液。

To establish a method for the determination of polymer impurities in cefixime raw materials and preparations,a cefixime degradation solution containing polymer impurities was prepared by forced polymerization.Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MS^n method.A new RP-HPLC method for cefixime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.5%formic acid-water solution and 0.5%formic acid-acetonitrile solution.The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers,resulting in a poor specificity and poor quantitative accuracy.But when using the RP-HPLC method,three polymer impurities were detected with good specificity,sensitivity and robustness,including two cefixime dimers,and dehydrate dimer.Therefore,the described RP-HPLC method is suitable for the quality control of polymer impurities in cefixime,and cefixime degradation solution can be used as suitable solution for analysis of cefixime polymers.