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Synthesis of selected 14C radiolabelled compounds in recent investigations of new analytical method applied in accelerated drug development (EUMAPP).

Wojciech Łuniewski ,  Wojciech J. Szczepek 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


            Accelerator mass spectrometry (AMS) is a method for quantifying rare isotopes and is now being applied in biomedicine. It measures radioisotopes such as radiocarbon, with zepto- or attomole sensitivity and high precision and throughput, allowing safe human pharmacokinetic studies involving microgram doses, compounds possessing low bioavailability or toxicology studies where administered doses must be kept extremely low. It is used to study absorption, metabolism, distribution, binding, and elimination which can be the measure with high precision after appropriate sample definition. The main application of AMS in drug discovery and development will be in the analysis of 14-carbon. The great sensitivity of AMS analysis allow much lower amounts of 14C to be used than for conventional counting methods. This makes it easier to use 14C for in vitro , preclinical and clinical research programmes. AMS is a technology that should increase human and environmental safety as well as mark up new research directions.

            Increasing chemical complexity of new drug candidates results in need to develop innovative synthesis of carbon-14 labelled pharmaceuticals. Limited number of labeled precursors as well as short time-lines force chemists to develop new reagents or to adapt existing methods to labelled syntheses. Selected examples of sumatriptan and compound S 19812–1 syntheses conducted in PRI illustrate some of creative strategies used to overcome these synthetic problems.

            Examples of application of common small molecule reagent, such as carbon-14 lebelled potassium cyanide are presented. A few strategies for radiolabelling are also described including the degradation of target molecule for accessing necessary intermediate for synthesis of radiolabelled sumatriptan.


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Presentation: Oral at VI Multidyscyplinarna Konferencja Nauki o Leku, by Wojciech Łuniewski
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2008-04-07 13:40
Revised:   2009-06-07 00:48