AdipoR-Agonisten in der präventiven Dopingforschung: Synthese, Metabolismus und Nachweis

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The aim of this thesis was the development of detection methods for the two, up to now, solely known adipoR-agonists AdipoRon and 112254 as part of the preventive doping research. These substances are mimetics of adiponectin, an endogenous protein secreted by adipocytes. Both adiponectin and the adipoR-agonists were found to reduce triglyceride- and glucose levels in cells, and thus enhance insulin sensitivity, which shows that adipoR-agonists can potentially be used as pharmaceuticals for the treatment of diabetes mellitus type 2. Similar to adiponectin, adipoR-agonists increase mitochondria-content in muscles via the AMPK-PPAR signaling pathway. The so-called ‘pseudo-exercise effect’ can potentially be abused by cheating athletes. Therefore, it is important to investigate these substances as part of preventive doping research. For the detection of the analytes, different biological matrices were employed. Mass spectrometric analysis was used by means of both well-established and state-of-the-art technologies in doping control analysis. Matrices used in this thesis were human blood plasma, urine and whole-blood by means of dried blood spots. While human plasma and urine are well-established matrices in doping control analysis, DBS analysis is a relatively new, easy und promising way of sampling and sample analysis. For a comprehensive detection, especially from urine, studies for the identification of metabolites of AdipoRon and 112254 were conducted both in vitro and in vivo. Summarizing, the work done in this thesis enables the mass spectrometric detection of the adipoR-agonists in different biological human matrices as part of the doping control analysis. The present assays are fully validated following WADA-guidelines and can be applied to samples of athletes, detecting the use of these new substances for performance enhancement. Furthermore, this work will protect clean athletes while also preserve the integrity of sports.
Original languageGerman
Place of PublicationKöln
PublisherDeutsche Sporthochschule Köln
Number of pages126
Publication statusPublished - 23.02.2018

ID: 3251065

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