Universität zu Köln

Dib, Josef, Schloerer, Nils ORCID: 0000-0002-0990-9582, Schaenzer, Wilhelm and Thevis, Mario (2015). Studies on the collision-induced dissociation of adipoR agonists after electrospray ionization and their implementation in sports drug testing. J. Mass Spectrom., 50 (2). S. 407 - 418. HOBOKEN: WILEY-BLACKWELL. ISSN 1096-9888

Full text not available from this repository.

Abstract

AdipoR agonists are small, orally active molecules capable of mimicking the protein adiponectin, which represents an adipokine with antidiabetic and antiatherogenic effects. Two adiponectin receptors were reported in the literature referred to as adipoR1 and adipoR2. Activation of these receptors stimulates mitochondrial biogenesis and results in an improved oxidative metabolism (via adipoR1) and increased insulin sensitivity (via adipoR2). Hence, adipoR agonists are potentially performance enhancing substances and targets of proactive and preventive anti-doping measures. In this study, two adipoR agonists termed AdipoRon and 112254 as well as two isotopically labeled internal standards (ISTDs) were synthesized in three-step reactions. The products were fully characterized by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) computation. Collision-induced dissociation pathways following electrospray ionization were suggested based on the determined elemental compositions of product ions, comparison to product ions derived from labeled analogs (ISTDs), H/D-exchange experiments and the results of DFT calculations. The most abundant product ions were found at m/z 174, tentatively assigned to protonated 1-benzyl-1,2,3,4-tetrahydropyridine for AdipoRon, and m/z 207, suggested as protonated 1-(4-methoxybenzyl)piperazine, for 112254. Notably, the loss of the heterocyclic ring (i.e. piperazine and piperidine, respectively) in a supposedly intramolecular elimination reaction was observed in both cases. A qualitative determination of both AdipoR agonists in human plasma was established and fully validated for doping control purposes. Validation items such as recovery (86-89%), specificity, linearity, lower limit of detection (1ng/ml), intraday (3-18%) and interday (5-16%) precision as well as ion suppression or enhancement were determined. Based on these findings adipoR agonists can be implemented in sports drug testing procedures. Copyright (c) 2015 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dib, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloerer, Nils UNSPECIFIED orcid.org/0000-0002-0990-9582 UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-412939
DOI:	10.1002/jms.3545
Journal or Publication Title:	J. Mass Spectrom.
Volume:	50
Number:	2
Page Range:	S. 407 - 418
Date:	2015
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1096-9888
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED PROTEIN-KINASE; ADIPONECTIN RECEPTORS; OBESITY; CLONING Multiple languages Biochemical Research Methods; Chemistry, Analytical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41293