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Determination of metabolic stability of positron emission tomography tracers by LC-ESI-MS/MS: an example in WAY-100635 and two analogues
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
In: Journal of Pharmaceutical and Biomedical AnalysisArticle in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-92492OAI: oai:DiVA.org:uu-92492DiVA: diva2:165596
Available from: 2005-01-11 Created: 2005-01-11Bibliographically approved
In thesis
1. Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices: Exploration of Radiotracer Chemistry as an Analytical Tool
Open this publication in new window or tab >>Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices: Exploration of Radiotracer Chemistry as an Analytical Tool
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Liquid chromatography – mass spectrometry (LC-MS) methods were developed for the analysis of positron emission tomography (PET) radiotracers in biological matrices. Additionally, radiotracer chemistry was explored as an analytical tool for supporting LC-MS method development and imaging molecular interactions in miniaturised chemical analysis systems.

Conventional radiodetection methods can offer high sensitivity in the analysis of radiotracers in biological matrices, although with the short half-life of PET tracers, this mass sensitivity decreases rapidly with time. This limits the time frame for analysis, and may compromise the precision and accuracy of the later measurements. Performing LC-MS analysis of the dominant stable isotope form of the tracer removes such time restrictions.

An LC-MS/MS method was developed for determination of the tracer flumazenil in human plasma, with high inter-assay precision (RSD < 7%) and accuracy (95 – 104%). The method was applied in a multiple scan PET study where the plasma concentration spanned from 0.07 to 0.21 nM. The method removed the time restrictions associated with radiodetection methods and thus provided the opportunity of analysing a greater number of samples than would have been possible with radioanalysis.

Furthermore, an LC-MS/MS method was developed that provided an efficient metabolic screening tool of potential PET tracers, whereby the substrates could be collected directly from 11C-labelling batches. This permitted repeated incubation experiments without the need of repeated labelling syntheses. A para-methoxy-benzamide analogue of the radiotracer WAY-100635 was thus identified as a potential tracer with improved metabolic stability. Additionally, a capillary LC-MS method was developed with rapid (0.75 min) and efficient (> 99%) on-line high flow-rate extraction for determination of metabolic stability of PET radiotracers.

Finally, the concept of radionuclide imaging of miniaturised chemical analysis systems was demonstrated with the direct study of interactions within capillary extraction columns and microchannels moulded in a plastic CD and poly(dimethylsiloxane).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 61 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 2
Analytical chemistry, liquid chromatography - mass spectrometry, radiotracer chemistry, positron emission tomography, biological samples, radionuclide imaging, Analytisk kemi
National Category
Analytical Chemistry
urn:nbn:se:uu:diva-4727 (URN)91-554-6126-3 (ISBN)
Public defence
2005-02-04, B42, BMC, Uppsala, 10:15
Available from: 2005-01-11 Created: 2005-01-11Bibliographically approved

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