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Liquid chromatography-mass spectrometry in the analysis of radiolabelled compounds for positron emission tomography

by Hyllbrant Forngren, Benita

Abstract (Summary)
Methods for liquid chromatography-mass spectrometry (LC/MS) with electrospray ionization (ESI) have been developed for the determination of specific radioactivity and for metabolic studies of radiolabelled compounds used in positron emission tomography (PET). These compounds often provide an analytical challenge mainly due to their low concentrations in complex sample matrices.The effect on sensitivity using different mobile phase additives, such as trifluoroacetic acid and formic acid, was investigated. The ESI-MS response shows higher stability and sensitivity when volatile additives are used. For reversed phase ion-pair chromatography separations, however, non-volatile counter-ions are used that destabilize the detector response and reduce the sensitivity. A method was therefore developed for on-line removal of the ion-pairing reagents prior to detection. Packed capillary columns and on-column focusing were used to improve mass sensitivity when analysing limited sample amounts. A commercial interface was modified to assist electrospray ionization at the low flow-rates (1 ?l/min) required by columns with an inner diameter of 200 µm. LC-MS methods were developed for determination of specific radioactivity of compounds labelled with short-lived radionuclides (i.e. 11C with T½=20.3 min and 76Br T½=16.2 h). In comparison with UV absorption detection, ESI-MS showed equal or improved sensitivity for all compounds investigated. The sensitivity of the developed methods allowed for detection of the radiolabelled isotope directly by mass spectrometry.A packed capillary LC/MS method was developed for determination of raclopride in plasma samples taken from patients during PET studies after intravenous injection of nanomolar doses. The validated assay exhibited satisfactory accuracy and precision over the concentration range 0.2-15 nM.
Bibliographical Information:

Advisor:

School:Uppsala universitet

School Location:Sweden

Source Type:Doctoral Dissertation

Keywords:NATURAL SCIENCES; Chemistry; Chemistry; Kemi; Analytical Chemistry; analytisk kemi

ISBN:91-554-4810-0

Date of Publication:01/01/2000

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