头孢氨苄原料的聚合物杂质分析  

Analysis of Polymer Impurities in Cephalexin Raw Material

作　　者：符雅楠 李进[1] 冯芳[2] 尹利辉[1] 姚尚辰[1] FU Ya-nan;LI Jin;FENG Fang;YIN Li-hui;YAO Shang-chen(National Institutes for Food and Drug Control,Beijing 102629,China;China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]中国药科大学,南京211198

出　　处：《中国药学杂志》2023年第4期365-375,共11页Chinese Pharmaceutical Journal

摘　　要：目的建立头孢氨苄原料中聚合物杂质的分析方法。方法采用非水溶剂碱降解法制备头孢氨苄强制降解溶液;采用高效分子排阻色谱法(HPSEC)和柱切换-液相色谱质谱联用法(LC-MSn)对头孢氨苄强制降解溶液中的聚合物杂质进行分离和结构鉴定,并评估HPSEC分离聚合物杂质的专属性;采用BDS HypersilTM型色谱柱以磷酸盐缓冲液(pH=5.0)-甲醇为流动相进行梯度洗脱,建立头孢氨苄聚合物的反相高效液相色谱法(RP-HPLC),并进行方法学验证。结果在头孢氨苄强制降解溶液中检出头孢氨苄二聚体及其异构体、三聚体和四聚体杂质;HPSEC分离头孢氨苄聚合物杂质时,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较差;RP-HPLC分析头孢氨苄聚合物杂质时,能够检出4种头孢氨苄指针性聚合物杂质,专属性好。结论采用HPSEC不能对头孢氨苄的聚合物杂质进行有效质控,建立的RP-HPLC分析头孢氨苄聚合物杂质时专属性良好、灵敏度高、方法耐用性好,可用于头孢氨苄原料的聚合物杂质质控,其中,头孢氨苄强制降解溶液可作为头孢氨苄聚合物分析的系统适用性溶液。OBJECTIVE To establish a method for the determination of polymer impurities in cephalexin raw material.METHODS Cephalexin stress solution was prepared by non-aqueous solvent alkali degradation method,polymer impurities in cephalexin stress solution were separated and structurally identified by high performance molecular exclusion chromatography(HPSEC)and column switching-LC/MSn,and the specificity of high performance gel chromatography for the separation of polymer impurities was assessed.A reversed-phase high performance liquid chromatography(RP-HPLC)analytical method for cephalexin polymer was established by gradient elution using phosphate buffer(pH=5.0)-methanol as mobile phase on a BDS HypersilTM column,and methodological validation was performed.RESULTS Cephalexin dimer,its isomer,trimer and tetramer impurities were detected in cephalexin stress solution.Small molecule impurities and polymer impurities co-appeared when cephalexin polymer impurities were separated by HPSEC,and the specificity and quantitative accuracy of the method were poor.Four cephalexin pointer polymer impurities could be detected when cephalexin polymer impurities were analyzed by RP-HPLC,with good specificity.CONCLUSION HPSEC method cannot effectively control the polymer impurities of cephalexin.The established RP-HPLC method has good specificity,high sensitivity and good robustness in the analysis of cephalexin polymer impurities,which can be used for the quality control of polymer impurities of cephalexin raw material.Cephalexin stress solution can be used as the system suitability solution for the analysis of cephalexin polymer.

关 键 词：头孢氨苄 聚合物 杂质 柱切换-液质联用法 高效分子排阻色谱 二维液相色谱 Β-内酰胺类抗生素 

分 类 号：R917[医药卫生—药物分析学]