在药物早期临床研究中加速器质谱的应用研究现状

Recent advances of accelerator mass spectrometry in clinical drug development

加速器质谱(AMS)是一种超灵敏同位素分析技术,近年来被广泛用于药物临床研发中14C标记药物的测定,且无需传统人体放射性研究相关的安全性试验。在药物早期临床试验阶段,加速器质谱有利于开展微剂量及微量示踪研究,从而尽早获得药物药代动力学及代谢特征,包括基本药代动力学参数(清除率、表观分布容积)、绝对生物利用度、物料平衡和消除途径等。本文就AMS的研究进展及其在药物早期临床研究中的应用做一综述。

Accelerator mass spectrometry （AMS） is a sensitive isotope ratio technique used in drug development that allows for small levels of 14C- drug to be administered to humans, thereby removing regulatory hurdles associated with radiotracer studies. It has facilitated the adoption of a human microdosing and microtracer studies in the early phase of clinical drug development. Studies using AMS and labeled compounds can provide pharmacokinetic and metabolism data, including： fundamen- tal pharmacokinetics （ clearance rate and apparent distribution volume）, absolute bioavailability, mass balance, routes and rates of excretion, metabolic fat. This review focuses on the advance progress of AMS as well as its roles in the early phase of clinical drug development.