Improved radiometabolite analysis procedure for positron emission tomography (PET) radioligands using a monolithic column coupled with direct injection micellar/high submicellar liquid chromatography.

A high-speed and high-sensitive direct plasma radiometabolite analysis method for positron emission tomography (PET) radioligands has been developed. It was based on micellar/high submicellar liquid chromatography (LC) using a semi-preparative alkyl-bonded silica rod column in conjunction with steep gradient and high flow rate for rapid macromolecule removal from plasma without significant sample preparation and fast/efficient separation of PET radioligands from their radiometabolites. Excellent separation of target PET radioligand from its radiometabolites was achieved within 4 min with a limit of detection of 1 Bq (Bq) level. This method was successfully applied to study the radiometabolism for a wide variety of (11)C and (18)F labeled radioligands in human or monkey plasma. The improved sensitivity and throughput permitted the analysis of a large number of plasma samples for accurate determination PET radioligands during quantitative PET imaging studies. Micellar/high submicellar LC together with a monolithic column is an attractive alternative method to determine the radiometabolism of PET radioligands in plasma.