摘要
目的:建立注射用头孢地嗪钠聚合物杂质的分析方法。方法:采用YMC-pack ODS-A(150 mm×4.6 mm,5μm)色谱柱,以0.01 mol·L^(-1)乙酸铵溶液-乙腈(950∶50)为流动相A,以乙腈为流动相B,梯度洗脱;采用TSKgel G2000SW(60 cm×7.5 cm,10μm)色谱柱,以磷酸盐缓冲液(pH 7.0)-乙腈(95∶5)为流动相;以2种色谱方法以及柱切换-LC-MS法对聚合物杂质含量较高的样品进行杂质分离和结构推导,并评估分子排阻色谱法分离聚合物杂质的专属性。采用YMC-pack ODS-A色谱柱,以磷酸盐溶液(A)-乙腈(B)为流动相,梯度洗脱,用于检测聚合物含量。结果:在头孢地嗪钠原料药、自制制剂和参比制剂中鉴定出5个聚合物杂质,分子量介于主成分与二聚体之间,其中4个未见文献报道,未发现二聚物以上的多聚物;分子排阻色谱法分离头孢地嗪钠聚合物时,易受到小分子杂质的干扰,方法专属性差;得到1种RPHPLC分析方法,能够检出排阻色谱得到的所有聚合物杂质,专属性良好,使用该方法检测聚合物总含量,结果为0.26%。结论:分子排阻色谱法不能对注射用头孢地嗪钠的聚合物杂质进行有效质控,建立的反相色谱法专属性良好,可作为日常质量控制的分析方法。
Objective:To establish an analytical method for polymer impurities in cefodizime sodium for injection.Methods:A YMC-pack ODS-A chromatographic column(150 mm×4.6 mm,5μm)was utilized with 0.01 mol·L^(-1) ammonium acetate solution-acetonitrile(950∶50)as mobile phase A and acetonitrile as mobile phase B,using gradient elution.Additionally,a TSKgel G2000SW chromatographic column(60 cm×7.5 mm,10μm)was used with phosphate buffer solution(pH 7.0)-acetonitrile(95∶5)as the mobile phase.These two chromatographic methods,along with a column-switching LC-MS method,were applied for the separation and structural elucidation of polymer impurities in samples with high polymer impurity content.The specificity of molecular exclusion chromatography for separating polymer impurities was also evaluated.A YMC-pack ODS-A column was used with phosphate buffer solution as mobile phase A and acetonitrile as mobile phase B,using gradient elution to detect polymer content.Results:Five polymer impurities with molecular weights between the main component and dimer were identified in cefodizime sodium bulk drug,self-made formulations,and reference formulations.Among them,four impurities had not been reported in literature,and no polymers larger than dimers were found.When using molecular exclusion chromatography to separate cefodizime sodium polymers,interference from small molecular impurities was observed,resulting in poor specificity.An RP-HPLC method was developed,capable of detecting all polymer impurities identified by molecular exclusion chromatography with good specificity.Using this method,the total polymer content was determined to be 0.26%.Conclusion:Molecular exclusion chromatography cannot effectively control polymer impurities in cefodizime sodium for injection.The established RP-HPLC method,with good specificity,can be used as an analytical method for routine quality control.
作者
涂海威
严萍
李亲泽
尹丹
TU Hai-wei;YAN Ping;LI Qin-ze;YIN Dan(Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Huizhou Sinlitai Pharmaceutical Co.,Ltd.,Huizhou 516211,China;Shenzhen Salubris Pharmaceuticals Co.,Ltd.,Shenzhen 518102,China)
出处
《药物分析杂志》
北大核心
2025年第4期727-738,共12页
Chinese Journal of Pharmaceutical Analysis
