Simultaneous determination of protein-free and total positron emission tomography radioligand concentrations in plasma using high-performance frontal analysis followed by mixed micellar liquid chromatography: application to [11C]PBR28 in human plasma

Analytical Chemistry
Ryuji NakaoChrister Halldin

Abstract

A two-dimensional liquid chromatographic (LC) system was developed for the determination of protein-free and total (free + bound forms) positron emission tomography (PET) radioligand concentrations in plasma by direct plasma injection. The unbound PET radioligand was first analyzed by high-performance frontal analysis using a short gel-filtration column and phosphate buffered saline solution as the mobile phase. All the collected effluent from the gel-filtration column was then transferred to the second dimension consisting of a monolithic C-18 column and mixed (anionic and nonionic surfactants) micellar eluent for determination of the total PET radioligand concentration. The simultaneous analysis of protein binding and radiometabolism of [(11)C]PBR28 was completed within 11 min without any pretreatment of plasma and employing a single analytical system. This system allowed highly sensitive analysis of total [(11)C]PBR28 with a limit of detection (LOD) of 1.6 becquerel (Bq). The LOD for the determination of unbound [(11)C]PBR28 was 21 Bq. Finally, simultaneous measurements of protein binding and radiometabolism of [(11)C]PBR28 in human plasma were achieved for up to 50 min after radioligand administration.

References

Apr 12, 1996·Journal of Chromatography. B, Biomedical Applications·A van WaardeW Vaalburg
Aug 17, 2002·Methods : a Companion to Methods in Enzymology·Marc LaruelleYiyun Huang
Dec 7, 2002·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Adriaan A Lammertsma
Jan 18, 2006·The Journal of Pharmacology and Experimental Therapeutics·Haritha MandulaQuentin R Smith

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