Universität zu Köln

Vogel, Matthias, Dib, Josef, Tretzel, Laura, Piper, Thomas ORCID: 0000-0002-7462-6693, Thomas, Andreas ORCID: 0000-0003-1199-0743, Schaenzer, Wilhelm and Thevis, Mario (2016). Analytics of nonpeptidic erythropoietin mimetic agents in sports drug testing employing high-resolution/high-accuracy liquid chromatography-mass spectrometry. Anal. Bioanal. Chem., 408 (23). S. 6431 - 6443. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1618-2650

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Abstract

Since its release as anti-anemic drug, recombinant erythropoietin (rEPO) gradually entered the illicit way to sports competitions as endurance-enhancing drug. Novel modifications biopharmaceutically introduced into the rEPO molecule in the form of carbohydrate or polyethylene glycol moieties made robust and sensitive test methods vital to doping controls in order to provide the necessary tools enabling the conviction of dishonest athletes. Modern protein analysis by means of gel electrophoretic separation and western blotting represents the status quo in rEPO anti-doping analysis. However, new therapeutically promising erythropoietin receptor activating compounds have been developed that exhibit cytokine hormone-mimicking properties but lack any protein structure. Progression to evade parenteral application and substitute for rEPO by low molecular mass and orally available compounds is still one of the major objectives in pharmaceutical research. In this approach, four promising in-house synthesized nonpeptidic erythropoietin mimetic agents, namely compound 129, compound 163, A1B10C1, and A5B10C4 were thoroughly evaluated by employing high-resolution/high-accuracy liquid chromatography tandem mass spectrometry experiments. Characteristic product ions were determined supporting the identification of these drugs and putative metabolites as well as related compounds in future doping controls. Test methods employing direct urine injection and receptor affinity purification strategies were assessed, which demonstrated that EPO receptor purification is of limited utility for nonpeptidic EPOR agonists while direct urine injection allowed for comprehensive method characterization. Thereby, achieved limits of detection were 1 ng/mL for compounds 129/163 and 5 ng/mL for A1B10C1/A5B10C4.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vogel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Dib, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Tretzel, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Piper, Thomas UNSPECIFIED orcid.org/0000-0002-7462-6693 UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-264902
DOI:	10.1007/s00216-016-9761-z
Journal or Publication Title:	Anal. Bioanal. Chem.
Volume:	408
Number:	23
Page Range:	S. 6431 - 6443
Date:	2016
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1618-2650
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VITRO; RECEPTOR; METABOLITES; URINE; BLOOD Multiple languages Biochemical Research Methods; Chemistry, Analytical Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26490