Study of the photocatalytic transformation of synephrine: a biogenic amine relevant in anti-doping analysis

The occurrence of some cases of positive results in anti-doping analysis of octopamine requires clarification as to whether its methylated derivative synephrine could be a metabolic precursor of octopamine itself. Synephrine is a natural phenylethylamine derivative present in some food supplements containing Citrus aurantium, permitted in sport regulations. A simulative laboratory study had been done using a photocatalytic process, to identify all possible main and secondary transformation products, in a clean matrix; these were then sought in biological samples obtained from three human volunteers and four rats treated with synephrine; the parent compound and its new potential metabolic products were investigated in human urine and rat plasma samples. The transformation of synephrine and octopamine and the formation of intermediate products were evaluated, adopting titanium dioxide as photocatalyst. Several products were formed and characterized using the HPLC-HRMS(n) technique. The main intermediates identified in these experimental conditions were compared with the major synephrine metabolites found in in vivo studies on rats and humans. Some more oxidized species, already formed in the photocatalytic process, were also found in urine and plasma samples of treated animals. These new findings could be of interest in further metabolism studies. The main photocatalytic pathway involving synephrine appears to be N-demethylation to give octopamine. On the contrary, we demonstrate the inconsistency of this reaction in both rat and human in vivo determinations, resulting in forensic importance.