Determination of Synthetic Impurities and Metabolic Products of F-ADAM, a Positron Emission Tomography Imaging Agent for Serotonin Transporter (SERT) Using HPLC-Tandem Mass Spectrometry
2020
A high performance liquid chromatography tandem mass
spectrometry (HPLC-MS/MS) analytical method was developed to determine the
identity of impurities resulting from the synthesis of N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzyl-amine
(F-ADAM), as well as its metabolic products by rat liver microsomes. 18F-ADAM
is an important positive electron emission ligand commonly employed as a
radio-imaging agent for serotonin transporter (SERT) in the brain. F-ADAM and
its derivatives were separated using HPLC on a C4-phenyl column with an
ammonium formate aqueous buffer/acetonitrile programmed mobile phase. Synthetic
contaminants and metabolic products were identified using fragmentation spectra
obtained by tandem mass spectrometry. We show that F-ADAM is unstable in
methanol, and propose the use of acetonitrile to generate optimal chromatogram.
A Cl-substituted species was found to be the major impurity resulting from the
F-ADAM synthetic process. The metabolic products
of F-ADAM by rat liver microsomes were characterized by oxidization of the
sulfur moiety to sulfoxide, demethylation of the dimethylamine moiety,
and oxidative defluorination/deamination. These results elucidate the
by-products of F-ADAM synthetic and metabolic processes, and provide direction
for the application of this imaging agent to biosystems properly.
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