APPLICATION OF LIQUID-CHROMATOGRAPHY COMBINED WITH MASS-SPECTROMETRY (LC-MS) TO ESTABLISH IDENTITY AND PURITY OF PET-RADIOPHARMACEUTICALS

This article describes the application of liquid chromatography combin ed with mass-spectrometry (LC-MS) as a new quality control tool for PE T-radiopharmaceuticals. The final step in the production of 2-[F-18]fl uoro-2-deoxy-D-glucose (F-18-FDG) is a purification by HPLC. This proc edure was validated by liquid chromatography combined with mass-spectr ometry (LC-MS) using the same separation conditions. D-Glucose, mannos e and FDG were separated, identified and quantified. The specific acti vity of F-18-FDG was >37,000 GBq . mmol(-1). The concentration of D-gl ucose was 0.5-1.0 mg . mL(-1) and the concentration of mannose was < 1 0 mu g . mL(-1). In addition, mass-spectrometry did not reveal other p otential reaction products, like furfural or polymerized sugar derivat ives in the final product. Consequently, the HPLC-purified FDG meets t he USP requirements. Furthermore, LC-MS was applied to verify the iden tity of thymidine in [2-C-11]thymidine batches. In conclusion, LC-MS i s a valuable tool for the identification of side-reaction-products and the validation of HPLC purification procedures in the preparation of PET-radiopharmaceuticals and thereby may help to assure safe and well- characterized PET-radiopharmaceuticals.