Huskey Su-Er W, Li Wenkui, Mangold James B, Flarakos Jimmy
Department of Drug Metabolism & Pharmacokinetics, Novartis Institutes for Biomedical Research, One Health Plaza, East Hanover, NJ 07936, USA.
Bioanalysis. 2014 Mar;6(5):617-28. doi: 10.4155/bio.14.25.
A tiered approach to drug metabolite measurement and identification is often used industry wide to fulfill regulatory requirements specified in recent US FDA and European Medicines Agency guidance. Although this strategy is structured in its intent it can be customized to address unique challenges which may arise during early and late drug development activities. These unconventional methods can be applied at any stage to facilitate metabolite characterization.
Two case studies are described NVS 1 and 2. NVS 1: plasma concentrations, measured using a radiolabeled MS-response factor exploratory method, were comparable to those from a validated bioanalytical method. The NVS 2 example showed how in vitro analysis helped to characterize an unexpectedly abundant circulating plasma metabolite M3.
A tiered approach incorporating many aspects of conventional and flexible analytical methodologies can be pulled together to address regulatory questions surrounding drug metabolite characterization.
在整个行业中，通常采用分层方法进行药物代谢物的测量和鉴定，以满足美国食品药品监督管理局（FDA）和欧洲药品管理局近期指南中规定的监管要求。尽管该策略的意图是结构化的，但可以进行定制，以应对在药物研发早期和后期活动中可能出现的独特挑战。这些非常规方法可在任何阶段应用，以促进代谢物的表征。
描述了两个案例研究，即NVS 1和NVS 2。NVS 1：使用放射性标记的质谱响应因子探索性方法测量的血浆浓度与经过验证的生物分析方法测得的浓度相当。NVS 2的例子展示了体外分析如何有助于表征一种意外大量存在的循环血浆代谢物M3。
可以将包含传统和灵活分析方法诸多方面的分层方法结合起来，以解决围绕药物代谢物表征的监管问题。
