J Nucl Med. 2012; 53 (Supplement 1):527
Molecular Targeting Probes - Radioactive and Nonradioactive
Simplified analytical HPLC purification of [11C]-raclopride
Nick Van Laeken1,
Ken Kersemans1 and
Filip De Vos1
1 Laboratory Radiopharmacy, Gent, Belgium
Abstract No. 527
Objectives: Previous research has highlighted the synthesis of [11C]-raclopride by methylation of S(+)-O-desmethylraclopride. Mostly, [11C]-raclopride is purified on a (semi-)preparative HPLC column followed by additional steps to obtain an injectable radiopharmaceutical. We aimed at simplifying the purification and the final preparation of [11C]-raclopride using an analytical C18 column and non-toxic solvents compatible with IV solutions.
Methods: [11C]-raclopride is radiosynthetised by the bubbling method: gaseous methyl triflate is sent through a solution of 100 µg precursor in 200 µL acetone. The reaction is ended by addition of 800 µL 0.05M ammonium acetate buffer (pH6) and the solution is directly loaded on the column. All separations are performed using an analytical Alltech Alltima C18 column (5 µm 150x4,6 mm), a 1000 µL loop, a mobile phase (pH 6) consisting of 0,05M NH4-Ac buffer/EtOH: 70/30 (V/V) and a flow of 2 mL/min. The fraction containing [11C]-raclopride is collected for 2,5 minutes and diluted 1/3 with physiological saline.
Results: [11C]-raclopride elutes after 10,6 minutes and is separated at baseline level from its precursor. The final solution (15 mL) contains 10% EtOH, suitable for injection. By using an analytical rather than a semi-preparative HPLC column and a solvent suitable for injection, additional purification steps, to reduce the concentration of residual solvents in the final formulation, can be avoided. In our module, the total purification time is reduced from 22 to 12 minutes.
Conclusions: By using an analytical C18 column and 0,05 M NH4-Ac buffer/EtOH: 70/30 (V/V) as a mobile phase, the purification time is drastically reduced and [11C]-raclopride, with a high specific activity and radiochemical purity, is obtained which only requires dilution with isotonic saline before administration to the patient
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Quality Control of the production and analytical HPLC purification of [11C]-Raclopride|
LOD desmethylraclopride:0.23 µg/mL raclopride:0.21 µg/mL LOQ desmethylraclopride:0.35 µg/mL raclopride:0.71 µg/mL