Universität zu Köln

Hansson, Annelie, Thevis, Mario, Cox, Holly, Miller, Geoff, Eichner, Daniel, Bondesson, Ulf and Hedeland, Mikael (2017). Investigation of the metabolites of the HIF stabilizer FG-4592 (roxadustat) in five different in vitro models and in a human doping control sample using high resolution mass spectrometry. J. Pharm. Biomed. Anal., 134. S. 228 - 237. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1873-264X

Full text not available from this repository.

Abstract

FG-4592 is a hypoxia-inducible factor (HIF) stabilizer, which can increase the number of red blood cells in the body. It has not been approved by regulatory authorities, but is available for purchase on the Internet. Due to its ability to improve the oxygen transportation mechanism in the body, FG-4592 is of interest for doping control laboratories, but prior to this study, little information about its metabolism was available. In this study, the metabolism of FG-4592 was investigated in a human doping control sample and in five in vitro models: human hepatocytes and liver microsomes, equine liver microsomes and S9 fraction and the fungus Cunninghamella elegans. By using liquid chromatography coupled to a Q-TOF mass spectrometer operated in MSE and MSMS modes, twelve different metabolites were observed for FG-4592. One monohydroxylated metabolite was detected in both the human and equine liver microsome incubations. For the fungus Cunninghamella elegans eleven different metabolites were observed of which the identical monohydroxylated metabolite had the highest response. This rich metabolic profile and the higher levels of metabolites produced by Cunninghamella elegans demonstrates its usefulness as a metabolite producing medium. In the doping control urine sample, one metabolite, which was the result of a direct glucuronidation, was observed. No metabolites were detected in neither the human hepatocyte nor in the equine liver S9 fraction incubates. (C) 2016 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hansson, Annelie UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Cox, Holly UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Geoff UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichner, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bondesson, Ulf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedeland, Mikael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-239949
DOI:	10.1016/j.jpba.2016.11.041
Journal or Publication Title:	J. Pharm. Biomed. Anal.
Volume:	134
Page Range:	S. 228 - 237
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1873-264X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRUCTURAL ELUCIDATION; PHASE-I; CUNNINGHAMELLA; IDENTIFICATION; EQUINE; AGENT Multiple languages Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23994