头孢他啶原料及制剂的聚合物杂质分析  

Analysis of polymer impurities in ceftazidime raw materials and preparations

作　　者：李进[1] 姚尚辰[1] 尹利辉[1] 许明哲[1] 胡昌勤[1] LI Jin;YAO Shang-chen;YIN Li-hui;XU Ming-zhe;HU Chang-qin(National Institutes for Food and Drug Control,Beijng 102629,China)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《药学学报》2020年第8期1889-1896,共8页Acta Pharmaceutica Sinica

摘　　要：建立头孢他啶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他啶降解溶液;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0.02 mol·L-1磷酸盐缓冲液-甲醇-乙腈为流动相,进行梯度洗脱,建立RP-HPLC法分析头孢他啶聚合物,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他啶聚合物杂质时,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法分析头孢他啶聚合物杂质时,在25~45 min内检出头孢他啶二聚体及其衍生物、三聚体等4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法可用于头孢他啶的聚合物杂质质控。头孢他啶降解溶液可作为分析头孢他啶聚合物的系统适用性溶液。To establish a method for the determination of polymer impurities in ceftazidime raw materials and preparations,a ceftazidime 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-MSnmethod.A new RP-HPLC method for ceftazidime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.02 mol·L-1 phosphate buffer,methanol and acetonitrile.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,four polymer impurities were detected in the 25-45 min time range with good specificity,sensitivity and robustness,including two ceftazidime dimers,trimers,and derivatives.Therefore,the described RP-HPLC method is suitable for the quality control of polymer impurities in ceftazidime,and ceftazidime degradation solution can be used as suitable solution for analysis of ceftazidime polymers.

关 键 词：头孢他啶 聚合物 杂质 柱切换-LC-MSn 高效凝胶排阻色谱 Β-内酰胺抗生素 

分 类 号：R917[医药卫生—药物分析学]