title: 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.
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.
authors: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institute , Stockholm, Sweden.
authors: Ryuji
authors: R
authors: Nakao
authors: Nahid
authors: N
authors: Amini
authors: Christer
authors: C
authors: Halldin
mesh_terms: D000081:Acetamides / Q000032:analysis*; D002250:Carbon Radioisotopes / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D008823:Micelles; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000032:analysis*; D011869:Radioligand Assay / Q000379:methods*
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D008823:Micelles; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines