Mass spectrometric identification and characterization of urinary metabolites of isopropylnorsynephrine for doping control purposes.

Isopropylnorsynephrine (isopropyloctopamine, deterenol, 4-(1-hydroxy-2-(isopropylamino)ethyl)phenol), a beta-selective and direct-acting adrenergic agonist, has been reported in the past as declared as well as non-declared ingredient of dietary supplements. The proven biological activity and the structural similarity of isopropylnorsynephrine to substances classified as prohibited compounds according to the World Anti-Doping Agency's (WADA's) regulations could necessitate the inclusion of this sympathomimetic amine into routine doping control analytical assays. Therefore, information on urinary metabolites is desirable in order to allow for an efficient implementation of target compounds into existing multi-analyte testing procedures, enabling the unequivocal identification of the administration of isopropylnorsynephrine by an athlete. In a pilot study setting, urine samples were collected prior to and after the oral application of ca. 8.7 mg of isopropylnorsynephrine, which were subjected to liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The intact drug, hydroxylated and/or glucurono- or sulfo-conjugated isopropylnorsynephrine were detected up to 48 h post-administration, with isopropylnorsynephrine sulfate representing the most abundant urinary target analyte. No relevant amounts of the dealkylation product (octopamine) were observed, indicating that merely moderate adaptations of existing test methods (or data evaluation strategies) are required to include isporpoylnorsynephrine in antidoping analytics, if required.