title: Rapid metabolite analysis of positron emission tomography radioligands by direct plasma injection combining micellar cleanup with high submicellar liquid chromatography with radiometric detection.
abstract: A column-switching liquid chromatographic (LC) system was developed for the radiometabolite analysis of positron emission tomography (PET) radioligands in plasma employing direct injection. This system involves (1) micellar cleanup using a short capture column with a micellar mobile phase for submitting plasma directly into the system, (2) fast-micellar liquid chromatography utilizing a small particle size (2.5 μm) analysis column under high submicellar condition for improving sensitivity, resolution and speed of analysis and (3) highly sensitive flow-through β(+) detection for online measurement of radioligands and their radiometabolites. This system enabled highly sensitive radiometric analysis at the lowest detection limit of about 1 Becquerel (Bq) for (11)C-labelled compounds with a high temporal resolution of <4.0 min without any pre-treatment of plasma. Finally, this novel method could be successfully applied to study the radiometabolism for various PET radioligands and provided reliable determination in both human and monkey plasma.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm, Sweden. ryuji.nakao@ki.se
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakao
authors.forename: Magnus
authors.initials: M
authors.lastname: Schou
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D000882:Haplorhini; D006801:Humans; D007275:Injections, Intravenous; D008823:Micelles; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity
chemical_list: D000097:Acetonitriles; D008823:Micelles; D019275:Radiopharmaceuticals; C032159:acetonitrile