注射用青霉素钠的聚合物杂质分析  

Analysis of polymer impurities in penicillin sodium for injection

作　　者：李进[1] 姚尚辰[1] 胡昌勤[1] LI Jin;YAO Shang-chen;HU Chang-qin(National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《中国新药杂志》2023年第6期629-637,共9页Chinese Journal of New Drugs

基　　金：中国食品药品检定研究院化药所重点实验室课题资助项目“抗生素药物杂质分析技术平台的建立与应用”(1030050090129)。

摘　　要：目的:建立注射用青霉素钠中聚合物杂质的分析方法。方法:采用水为溶剂制备青霉素钠的聚合物杂质溶液;采用高效分子排阻色谱法(HPSEC)和柱切换-LC/MSn法对聚合物杂质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C_(18)型反相色谱柱,以[磷酸盐缓冲液溶液(pH 3.4)-甲醇(72∶14)]-乙腈为流动相进行梯度洗脱,建立RP-HPLC分析方法,并进行方法学验证。结果:在聚合物杂质溶液中鉴定出4种青霉素聚合物及其异构体,1种二聚体降解物以及若干小分子杂质;HPSEC法分离聚合物杂质时,小分子杂质与聚合物杂质共出峰,定量准确性与方法专属性差;RP-HPLC法分析能够检出3个指针性青霉素钠聚合物杂质峰,其中包含2种不同聚合方式形成的二聚体杂质。结论:HPSEC法不能对注射用青霉素钠的聚合物杂质进行有效质控,建立的RP-HPLC法分析注射用青霉素钠聚合物杂质的专属性良好、灵敏度高。Objective:To establish a method for determination of polymer impurities in penicillin sodium for injection.Methods:Penicillin sodium was dissolved by water to prepare penicillin polymer stock solution.High performance size exclusion chromatography method(HPSEC)and column switching-LC/MSn method were used to separate and deduce the weak retention impurities in polymer impurity solution and the specificity of HPSEC method was evaluated.A RP-HPLC method for polymer analysis was established with a C_(18) column,using gradient elution by the mixed solution[phosphate buffer solution(pH 3.4)-methanol(72:14)] and acetonitrile,and the RP-HPLC method was validated.Results:4 polymers,their isomers,one dimer degradation and some small molecular impurities were identified in the polymer impurity solution.Polymer impurities were liable to be co-eluted with small molecular impurities by HPSEC method,which resulted in poor quantification accuracy and specificity.3 indicative polymer impurities were detected by RP-HPLC method with effective specificity,including 2 dimers produced by different polymerized patterns.Conclusion:HPSEC cannot effectively control the polymer impurities of penicillin sodium for injection.The established RP-HPLC method has good specificity and high sensitivity for the determination of impurities in penicillin sodium polymerfor injection.

关 键 词：注射用青霉素钠 聚合物 杂质 柱切换-LC/MSn 高效凝胶色谱 二维色谱 Β-内酰胺抗生素 

分 类 号：R917[医药卫生—药物分析学]