a unique automation platform for measuring low level radioactivity in metabolite identification studies一个独特的自动化平台测量低水平放射性代谢物鉴定研究.pdfVIP

A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies 2 1 1 1 1 Joel Krauser *, Markus Walles , Thierry Wolf , Daniel Graf , Piet Swart 1 DMPK/Biotransformation Laboratories, Novartis Pharma AG, Basel, Switzerland, 2 DMPK/Isotope Laboratories, Novartis Pharma AG, Basel, Switzerland Abstract Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automa