Dib, Josef, Tretzel, Laura, Piper, Thomas, Lagojda, Andreas, Kuehne, Dirk, Schaenzer, Wilhelm and Thevis, Mario (2017). Screening for adiponectin receptor agonists and their metabolites in urine and dried blood spots. Clin. Mass Spectrom., 6. S. 13 - 21. AMSTERDAM: ELSEVIER. ISSN 2213-8005

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Abstract

AdipoRon and 112254 represent two known synthetic adiponectin receptor (adipoR) agonists. Although AdipoRon is the more potent compound, both have physiological properties that are similar to adiponectin - an adipokine with antidiabetic and antiatherogenic effects. Several transcriptional regulators are activated by adipoR-agonists leading to increased mitochondrial DNA content in vitro, an effect that can be abused by athletes for performance enhancing purposes. In the context of preventive anti-doping research, detection of AdipoRon and 112254 in routine doping control specimens would be valuable. Here, we describe our process for incorporating AdipoRon and 112254 into routine doping control methods involving urine and dried blood spot (DBS) analysis. Method validation including evaluation of specificity, limit of detection, identification capability, carryover, matrix interference, recovery, interday and intraday precision and linearity to standards provided by WADA. For identification in human urine, a liquid chromatography-tandem mass spectrometry-based testing approach was implemented for both adipoR agonists and two respective phase-I metabolites. Recovery of 85-104%, satisfactory limits of detection (i.e., 0.5-1 ng/mL), and imprecision values over three days at three concentration levels of < 19% demonstrated the assay's fitness-for-purpose. For identification from DBS a liquid chromatography-high-resolution/high-accuracy tandem mass spectrometry with online solid-phase extraction was implemented for AdipoRon and 112254. Here also, acceptable recoveries (i.e., 22-33%), limits of detection of 5-10 ng/mL, and imprecision values over three days at three concentration levels of < 23%, were demonstrated. Hence, two methods for doping control screening from urine and DBS were established and shown to be fit-for-purpose for routine use.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dib, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tretzel, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piper, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lagojda, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuehne, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaenzer, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thevis, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-210041
DOI: 10.1016/j.clinms.2017.10.002
Journal or Publication Title: Clin. Mass Spectrom.
Volume: 6
Page Range: S. 13 - 21
Date: 2017
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 2213-8005
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Medical Laboratory TechnologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21004

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