10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds—new analytical methods Session 8, Wednesday, June 17, 2009

Abstract

Different methods for the analysis of radiolabelled compounds are discussed as well as their potential uses in a wide range of activities such as drug discovery and ultra low level background LSC in a salt mine.Keywords: accelerator mass spectrometry; microdosing; optogalvanic spectroscopy; ultra-low level scintillation counting; radiosynthesis; microfluidics SOMETHING OLD, SOMETHING NEW-APPLICATIONS OF ACCELERATOR MASS SPECTROMETRY IN TRANSLATIONAL MEDICINE R COLIN GARNERXceleron Ltd, The Biocentre, Innovation Way, York YO10 5NY, United Kingdom and Hull York Medical School, University of York, York, YO10 5DD, United Kingdom Abstract: The enabling technology of accelerator mass spectrometry (AMS) permits ultrasensitive analysis of 14 C in the attogram to zeptogram range. As a result AMS analysis is being used in drug development to measure drug concentrations from human clinical studies conducted with very low amounts (nanoCuries) of administered radiolabel. The administered radiolabel can be at high specific radioactivity as in Phase 0 microdose studies or at much lower specific radioactivity as in metabolite profiling/mass balance and absolute bioavailability studies. Each of these study designs can give essential human ADME/PK information enabling drugs to be developed more effectively than using conventional approaches.Keywords: accelerator mass spectrometry; microdosing; ADME/PK; absolute bioavailability Introduction: Developing new drugs for the treatment of life threatening diseases is a costly and time consuming process. Bringing a new drug to market can take anywhere between 12-15 years and cost upwards of $1 billion.1 Research productivity by the pharmaceutical and biotechnology industries has been falling year on year even though R&D expenditures have exponentially increased.2 Indeed there were fewer new drug marketing approvals by the regulatory authorities last year than there were in the mid-90's. It has been estimated that the current R&D annual expenditure by the pharmaceutical industry is approximately $75 billion worldwide. Many of the blockbuster drugs are coming off patent and growth in revenues of some of the world's largest pharmaceutical companies have fallen back to historically low levels.3,4 Despite this crisis, large pharmaceutical companies still appear to be slow in adopting new approaches despite the US FDA encouraging innovation through it's Critical Path initiative.