Quality control of PET radiopharmaceuticals using HPLC with electrochemical detection

The usefulness of high-performance liquid chromatography with electrochemical detection (HPLC/ECD) in the quality control of positron emission tomography (PET) radiopharmaceuticals was evaluated for a number of substances. Chromatographic separation was performed using a reversed phase column and acetonitrile or 20 mM sodium phosphate buffer as the mobile phase. The effluent from the column was introduced into an electrochemical detector equipped with a glassy carbon electrode versus Ag/AgCl electrode operated in the direct current mode. In 19 of 21 PET radiopharmaceuticals studied, the compounds and corresponding precursors used in the synthesis of the radiopharmaceuticals could be successfully detected by the HPLC/ECD method. For 17 compounds with electroactive functional groups, such as aliphatic amines, phenols and aromatic amines, the detection limits were ppb levels for a 20-μl injection volume; this was significantly better compared with ultraviolet (UV) detection. This method could be applied to the analysis of [11C]MP4A, useful PET radiopharmaceutical for measuring acetylcholinesterase activity in the brain with no available UV absorbance.