注射用头孢西丁钠的聚合物杂质分析

Analysis of polymer impurities in cefoxitin sodium injection

目的:建立注射用头孢西丁钠聚合物杂质的分析方法。方法:采用水为溶剂制备头孢西丁钠聚合物浓溶液;采用高效凝胶色谱法(HPSEC,TSK G2000 SWxl)和柱切换-LC/MSn法对头孢西丁钠聚合物浓溶液的弱保留值杂质进行分离和结构鉴定,并评估HPSEC法分析聚合物杂质的专属性;采用Shimadzu Inertsil Ph-3型色谱柱,以磷酸盐缓冲液溶液(pH 3.2)-甲醇-乙腈为流动相进行梯度洗脱,建立头孢西丁钠聚合物的反相高效液相色谱(RP-HPLC)分析方法,并进行方法学验证。结果:在头孢西丁钠聚合物浓溶液中检出出头孢西丁钠聚合物杂质,以及4个小分子杂质;HPSEC法分离头孢西丁钠聚合物杂质时,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法分析头孢西丁钠聚合物杂质时,能够检出2种头孢西丁钠指针性聚合物杂质,专属性好。结论:HPSEC法不能对头孢西丁钠的聚合物杂质进行有效质控,建立的RP-HPLC法分析头孢西丁钠聚合物杂质的专属性良好,可将头孢西丁钠聚合物浓溶液作为聚合物杂质系统适用性溶液。

Objective:To establish a determination method of polymer impurities in cefoxitin sodium injection.Methods:Cefoxitin sodium was dissolved in water to prepare stock solution of cefoxitin sodium polymer.High performance size exclusion chromatography(HPSEC,TSK-gel G2000 SWxl)and column switching-LC/MSn were applied to separate and deduce the poor retention impurities in the stock solution and to evaluate the specificity of HPSEC method.A new RP-HPLC method for polymer analysis was established with a Shimadzu Inertsil Ph-3 column,using a gradient elution by phosphate buffer solution(pH 3.2)-acetonitrile-methanol,and the method was validated.Results:Several cefoxitin sodium polymers were identified in stock solution of cefoxitin sodium polymer,4 small molecular impurities were also detected.Polymer impurities were liable to co-elute with small molecular impurities by HPSEC method,making a poor quantification accuracy and specificity.Two indicative polymer impurities were detected by RP-HPLC method with an effective specificity.Conclusion:HPSEC method was not suitable for the quality control of polymer impurities in cefoxitin sodium injection,while the new established RP-HPLC method was specific,which could effectively control the polymer impurities.Cefoxitin sodium polymer stock solution could be used to identify polymer peaks as the system suitability solution.