氘代药物氘同位素纯度检测方法研究进展  

Recent advances in analytical techniques for deuterium isotopic purity of deuterated drugs

作　　者：黄逸文 李忠 鲁辉 吴杨 HUANG Yi-wen;LI Zhong;LU Hui;WU Yang(Suzhou Institute for Drug Control,Suzhou 215104,China;Yantai Key Laboratory of Nanomedicine&Advanced Preparations,Yantai Institute of Materia Medica,Yantai 264000,China)

机构地区：[1]苏州市药品检验检测研究中心,江苏苏州215104 [2]烟台药物研究所,烟台市纳米药物与高端制剂重点实验室,山东烟台264000

出　　处：《药学学报》2024年第5期1176-1185,共10页Acta Pharmaceutica Sinica

基　　金：国家药品标准制修订研究课题(2022Y09);江苏省市场监督管理局科技计划项目资助(KJ2024084);苏州市科技计划项目(SKYD2023165)。

摘　　要：氘代药物相比原型药物因具有改善药动学特性、减少毒性代谢产物、稳定手性结构等优势,已成为药物设计与开发的新策略。现代氘代合成技术仍不可避免地会生成氘同位素杂质(包括氘同位素异数体和氘同位素异构体),这些氘同位素杂质通过氘动力学同位素效应显著影响药物的安全性与有效性。因此,氘同位素纯度是氘代药物相比其他药物最为特征的关键质量属性。然而,同位素混合物在常规分析方法下难以分离,且目前尚无药品监管机构制定氘代药物分析检测和质量控制相关的指南,这使得氘代药物的开发在分析上面临着很大的挑战。本文对目前氘代药物同位素纯度检测技术的研究进展进行了综述,总结了不同方法的优缺点及应用范围,以期为氘代药物的开发和相关研究提供参考。Deuterated drugs have been new strategies in drug design and development for advantages in improving pharmacokinetic properties,reducing toxic metabolites,and stabilizing chiral structures over their nondeuterated counterparts.Deuterium isotopic impurities,including isotopologues and isotopomers,are inevitably generated even with state-of-the-art deuteration techniques,which significantly affect the safety and potency of drugs through deuterium kinetic isotope effects.Therefore,deuterium isotopic purity is the most characteristic critical quality attribute of deuterated drugs compared to other drugs.However,it is challenging to separate isotopic mixtures with routine analytical methods,and regulatory agencies have not proposed guidelines for deuterated drugs in terms of analytical techniques and quality control,which presents great analytical challenges for the development of deuterated drugs.This paper reviews the analytical techniques for deuterium isotopic purity of deuterated drugs and discusses the features and scopes of different methods.It aims to provide references for the development and relevant study of deuterated drugs.

关 键 词：氘代药物 氘同位素纯度 氘代率 质谱法 定量核磁共振波谱法 分子转动共振波谱法 

分 类 号：R917[医药卫生—药物分析学]