Atmospheric Pressure Electrospray Ionization Mass Spectra of Glucose and 2-Fluorodeoxyglucose for Quantitative Analysis of 2-Fluorodeoxyglucose by High-Performance Liquid Chromatography

Abstract

2-Fluoro-2-deoxy-d-glucose (FDG) labeled by fluorine-18 is the most widely used radiopharmaceutical for positron emission tomography (PET). For high-performance liquid chromatography (HPLC)/MS assay and quality control, the mass spectra of FDG and glucose (Glc) in organic + water solutions were studied by flow injection analysis (FIA) and in a chromatographic eluate. In acetonitrile (MeCN) + 0.025% ammonium formate (NH4HCO2) solvent (80: 20), electrospray ionisation (ESI) of glucose-FDG provides M.NH4+ and 2M.Na+ (M = Glc or FDG) as the most intense positive ions. Formation of the latter ions and also of M.MeCN.Na+ and 2MeCN.Na+ is typical of the presence of NaCl in the ESI inlet. The positive ions include heavier ions corresponding to the impurities separated by HPLC and also to the cross-ring fragmentation of complexes (2FDG. aMeCN–X)L, where a = 0 or 1, L is either Na+ or NH4+ and X is a fragmented pyranose or anhydropyranose residue. The second most abundant Glc negative ion is m/z = 359 which was interpreted as (2Glc–H+)−. The negative-ion spectrum of FDG has dominating lines due to FDG.HCO2− ions at m/z 227 and also (2FDG–H+)− at m/z 363. The m/z 363 signal is suppressed in the presence of NaCl at a molar ratio of 4:1 to NH4HCO2, while the ions at m/z 217 and 219, i.e. FDG.Cl−, become three times more intense than FDG.HCO2−. The latter ion appears to be most suitable as an analytical signal for chemical analysis of FDG at m/z 226 and 227. Limits of FDG quantitation ( LOQ) of 19 ng and 21 ng were found for the 200+ and 227− ion signals, respectively, and are wholly adequate for verification of total FDG content in radiopharmaceuticals.