亚叶酸钙杂质结构及降解途径研究  

Study on the Impurity Structure and Degradation Pathway of Calcium Folinate

作　　者：金一宝 汤佳 潘静 李美芳 王平 黄晓龙 王冰 Jin Yibao;Tang Jia;Pan Jing;Li Meifang;Wang Ping;Huang Xiaolong;Wang Bing(Shenzhen Institute for Drug Control,NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation,Shenzhen Key Laboratory of drug Quality Standard Research,Shenzhen 518057,China;Greater Bay Area Center for Drug Evaluation and Inspection of National Medical Products Administration,Shenzhen 518017,China)

机构地区：[1]深圳市药品检验研究院,国家药品监督管理局仿制药评价生物等效性研究重点实验室,深圳市药品质量标准研究重点实验室,广东深圳518057 [2]国家药品监督管理局药品审评检查大湾区分中心,广东深圳518017

出　　处：《广东化工》2024年第19期1-3,10,共4页Guangdong Chemical Industry

基　　金：国家药品监督管理局药品审评检查大湾区分中心监管科学课题(GBA-JGKX-001);国家药品标准制修订研究课题(2023Y03)。

摘　　要：亚叶酸钙是四氢叶酸的甲酰化衍生物,作为叶酸拮抗剂,临床上用治疗贫血及肿瘤。本文通过核磁技术对亚叶酸钙有关杂质的化学成分进行了结构分析,建立HPLC分析方法,考察氧化、酸、碱、高温、光照强制降解条件对亚叶酸钙原料药的影响,明确亚叶酸钙的主要降解途径为碱破坏、酸破坏和氧化破坏,为亚叶酸钙原料药及制剂的有关物质的研究提供依据。Calcium folinate is a formylated derivative of tetrahydrofolate,used as a folate antagonist in the clinical treatment for anemia and tumors.In this paper,the chemical composition of calcium folinate-related impurities was analyzed by nuclear magnetic resonance technology,and an HPLC analysis method was established to investigate the effects of oxidation,acid,base,high temperature,and light irradiation on the degradation of calcium folinate.The main degradation pathways of calcium folinate were determined to be base destruction,acid destruction and oxidative destruction.This experiment was conducted to simulate the degradation process of calcium folinate with a variety of environments involved in forced degradation.The study helps to explore the related substances for quality control of calcium folinate API and its formulations.

关 键 词：亚叶酸钙 降解杂质 结构解析 核磁 质谱 高效液相色谱仪 

分 类 号：R917[医药卫生—药物分析学]