寡核苷酸药物的质控关键技术研究  

Key Technologies for Quality Control of Oligonucleotide Drugs

作　　者：刘博 袁亚楠 王悦 程舒倩 卢治国 范慧红 孙会敏 LIU Bo;YUAN Yanan;WANG Yue;CHENG Shuqian;LU Zhiguo;FAN Huihong;SUN Huimin(Chemical Drug Control Institute of National Institutes for Food and Drug Control,Beijing 102629,China;NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing 102629,China;Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China)

机构地区：[1]中国食品药品检定研究院化学药品检定所,北京102629 [2]国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629 [3]中国科学院过程工程研究所,北京100190

出　　处：《中国药物警戒》2025年第1期1-9,共9页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(22205240);药品监管科学全国重点实验室课题(2024SKLDRS0222)。

摘　　要：目的全面梳理寡核苷酸药物的基本情况及其质控手段(尤其是有关物质分析技术),为更为精准控制寡核苷酸药物的产品质量提供参考。方法通过检索国内外相关文献及数据库,对寡核苷酸杂质分析、结构表征、精准定量等方面的研究进展进行整理、分析和归纳。结果已上市的寡核苷酸药物主要有反义寡核苷酸、小干扰核糖核酸和核酸适配体3类,质量控制主要参考国外相关指南,离子对反相色谱法、离子交换色谱法和质谱法常用于寡核苷酸药物质量控制,同时其他分析技术具有独特优势。结论寡核苷酸质量控制取得了较大进展,但在国内目前缺少针对性指导原则。另外,现有寡核苷酸药物分析方法仍存在一些问题。需深入研究,开发新方法,为寡核苷酸药物质量控制提供技术支撑。Objective To review the basic data and quality control methods of oligonucleotide drugs in order to provide a reference for quality control of oligonucleotide drugs.Methods By searching related literature and databases at home and abroad,the methods of analysis of related substances,structural characterization,and quantification of oligonucleotides were summarized.Results There were three types of oligonucleotide drugs that had been listed:antisense oligonucleotide,small interfering RNA,and aptamer.Their domestic quality control guidelines mainly referred to foreign guidelines.Ion-pair reverse phase chromatography,ion exchange chromatography,and mass spectrometry were commonly used for quality control of oligonucleotide drugs.Other analysis techniques had their own advantages.Conclusion Significant progress has been made in quality control of oligonucleotide drugs.However,China lacks specific guidelines.Furthermore,there are several problems with the current oligonucleotide drug analysis techniques.To offer strong technical support for quality control of oligonucleotide drugs,research and the development of novel techniques are required.

关 键 词：寡核苷酸 反义寡核苷酸 小干扰核糖核酸 核酸适配体 质量控制 有关物质 液相色谱法 质谱法 液质联用 

分 类 号：R917[医药卫生—药物分析学]