Further investigations into urinary higenamine – metabolite patterns and stability

Code: 22C05MT

Higenamine is a non-selective β2-agonist, which has been described as a key component of a great variety of natural plants such as Nandina domestica, Tinospora crispa, and Annona squamosa. Although higenamine has never been approved as a drug by the US Food and Drug Administration (FDA), it plays an important role in traditional Chinese herbal medicine (it has been approved for clinical research by the China Food and Drug Administration - CFDA), and has been found to be an ingredient - often unlabeled - of different weight loss and sports supplements, which has been suspected or proven to have caused cases of unintentional anti-doping rule violations.
Within the scope of a previous elimination study aiming at the urinary quantification of higenamine after administration of tropical fruit plants from the Annonaceae family, it could be shown that single-dose administrations of these fruit species are rather unlikely to lead to AAFs in sports. The aim of this project is to conduct further investigation which complement the previous datasey. For that purpose, stability evaluation of componuds of interest, and specific contribution of the different higenamine conjugates will be performed. Besides, two different administrations studies with a total of 6 healthy volunteers  (3 x ♂, 3 x ♀) are planned. Each participant will eat 3 servings on Annona fruit puree with 24 h (8:00 am, 6:00 pm, and next day 8:00 am) and, at after washout, a single dose of two different higenamine-containing nutritional supplements. Urine samples will be collected up to three days following administration in both study phases, and comprehensive analyses are planned to support result management and decision-making processes in case of higenamine findings in sports drug testing programs, preferably by means of new potential biomarkers of plant-derived higenamine administrations.