头孢地尼原料及制剂的聚合物杂质分析

目的 建立头孢地尼原料及制剂聚合物杂质的分析方法。方法 分别采用0.1mol/L磷酸盐溶液和氯仿-三乙胺为溶剂，制备头孢地尼降解溶液；采用高效凝胶色谱法(HPSEC, TSK G2000 SWxl)和柱切换-LC/MSn法对头孢地尼降解溶液的弱保留值杂质进行分离和结构鉴定，并评估高效凝胶色谱法分析聚合物杂质的专属性；采用Diamonsil, C18型色谱柱，以0.25%四甲基氢氧化铵溶液(pH5.5)-甲醇-乙腈为流动相进行梯度洗脱，建立头孢地尼聚合物的RP-HPLC分析方法，采用二维色谱法和柱切换-LC/MSn法对其专属性进行分析，并进行方法学验证。结果 在头孢地尼降解物中鉴定出头孢地尼二聚体及其异构体，以及若干小分子杂质；高效凝胶色谱法分离头孢地尼聚合物杂质时，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法分析头孢地尼聚合物杂质时，能够检出头孢地尼二聚体及其异构体，头孢地尼三聚体，专属性好。结论 高效凝胶色谱法不能对头孢地尼的聚合物杂质进行有效质控，建立的反相色谱法分析头孢地尼聚合物杂质的专属性良好，可将头孢地尼降解溶液可作为聚合物杂质系统适用性溶液。

Analysis of polymer impurities in cefdinir raw materials and preparations#br#

Objective To establish a method for the determination of polymer impurities in cefdinir raw materials and preparations. Methods Cefdinir raw materials were dissolved by a 0.1mol/L phosphate solution and the reagent chloroform-triethylamine respectively to prepare cefdinir degradation solutions. The High Performance Size Exclusion Chromatography (HPSEC, TSK-gel G2000SWxl) method and the Column Switching-LC/MSn method were applied to separate and identify the poor retention impurities in cefdinir degradation solutions and to evaluate the specificity of the HPSEC method. A new RP-HPLC method for polymer analysis was established with a Diamonsil C18 column, using a gradient elution by 0.25% tetramethylammonium hydroxide (pH5.5)-acetonitrile-methanol. The specificity of the RP-HPLC method was assessed by the two dimensional chromatography method and the Column Switching-LC/MSn method, and the RP-HPLC method was validated. Results Cefdinir dimer and isomers were identified in cefdinir degradation solutions, and some small molecular impurities were also detected. Polymer impurities were liable to co-elute with small molecular impurities by the HPSEC method, which made a poor quantification accuracy and specificity. Cefdinir dimer and isomers were detected by the RP-HPLC method with an effective specificity. Conclusion The HPSEC method is not suitable for the quality control of polymer impurities in cefdinir raw materials and productions, while the new established RP-HPLC method is specific, which can effectivelycontrol the polymer impurities. Cefdinir degradation solution can be used to identify polymer peaks as the system suitability solution.