Universität zu Köln

Thevis, Mario, Piper, Thomas ORCID: 0000-0002-7462-6693, Dib, Josef, Lagojda, Andreas, Kuehne, Dirk, Packschies, Lars, Geyer, Hans and Schaenzer, Wilhelm (2017). Mass spectrometric characterization of the selective androgen receptor modulator (SARM) YK-11 for doping control purposes. Rapid Commun. Mass Spectrom., 31 (14). S. 1175 - 1184. HOBOKEN: WILEY. ISSN 1097-0231

Full text not available from this repository.

Abstract

RATIONALE: Selective androgen receptor modulators (SARMs) represent an emerging class of therapeutics targeting inter alia conditions referred to as cachexia and sarcopenia. Due to their anabolic properties, the use of SARMs is prohibited in sports as regulated by the World Anti-Doping Agency (WADA), and doping control laboratories test for these anabolic agents in blood and urine. In order to accomplish and maintain comprehensive test methods, the characterization of new drug candidates is critical for efficient sports drug testing. Hence, in the present study the mass spectrometric properties of the SARM YK-11 were investigated. METHODS: YK-11 was synthesized according to literature data and three different stable-isotope-labeled analogs were prepared to support the mass spectrometric studies. Using high-resolution/high-accuracy mass spectrometry following electrospray ionization as well as electron ionization, the dissociation pathways of YK-11 were investigated, and characteristic features of its (product ion) mass spectra were elucidated. These studies were flanked by density functional theory (DFT) computation providing information on proton affinities of selected functional groups of the analyte. RESULTS AND CONCLUSIONS: The steroidal SARMYK-11was found to readily protonate under ESI conditions followed by substantial in-source dissociation processes eliminating methanol, acetic acid methyl ester, and/or ketene. DFT computation yielded energetically favored structures of the protonated species resulting from the aforementioned elimination processes particularly following protonation of the steroidal D-ring substituent. Underlying dissociation pathways were suggested, supported by stable-isotope labeling of the analyte, and diagnostic product ions for the steroidal nucleus and theD-ring substituent were identified. Further, trimethylsilylated YK-11 and its deuterated analogswere subjected to electron ionization high-resolution/high-accuracy mass spectrometry, complementing the dataset characterizing this new SARM. The obtained fragment ions resulted primarily from A/B- and C/D-ring structures of the steroidalnucleus, thus supporting future studies e.g. concerning metabolic pathways of the substance. Copyright (C) 2017 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Piper, Thomas UNSPECIFIED orcid.org/0000-0002-7462-6693 UNSPECIFIED Dib, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Lagojda, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehne, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Packschies, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Geyer, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-224591
DOI:	10.1002/rcm.7886
Journal or Publication Title:	Rapid Commun. Mass Spectrom.
Volume:	31
Number:	14
Page Range:	S. 1175 - 1184
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0231
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METABOLITES; DISCOVERY; CACHEXIA; FRAILTY; CANCER; YK11 Multiple languages Biochemical Research Methods; Chemistry, Analytical; Spectroscopy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22459