Rapid metabolite analysis of positron emission tomography radioligands by direct plasma injection combining micellar cleanup with high submicellar liquid chromatography with radiometric detection

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 11C-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.

► A simple column-switching LC method for the radiometabolite analysis in plasma.
► This system involves micellar cleanup of plasma and high submicellar fast-LC.
► No sample preparation is required.
► Metabolite analysis is completed within 4 min with high sensitivity.
► It provides reliable analysis of a large number of samples during PET studies.