Retracted: Detection of novel metabolite for Roxadustat doping by global metabolomics

Retracted: Detection of novel metabolite for Roxadustat doping by global metabolomics Summary Roxadustat (FG-4592, Rox) is a stabilizer for hypoxia-inducible transcription factors (HIFs), which induce production of the erythroid growth factor erythropoietin, and has been listed by the World Anti-Doping Agency as a prohibited substance for athletes since 2011. Although the detection technologies for Rox and its glucuronide-conjugated metabolite (Rox-Gluc) have been developed exploiting triple quadrupole mass spectrometry (MS/MS), the production of metabolites from Rox in the human body remains to be clarified. Here, we established a protocol for the detection of unknown metabolites in plasma and urine samples from Rox-doping mice by global metabolomics using an ultra high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). We identified methylated Rox (Rox-Methyl), a novel metabolite, and Rox-Gluc in mouse urine by principal component analysis and orthogonal partial least squares discriminant analysis based on detected features by UHPLC-QTOF/MS analysis. The estimated pharmacokinetic parameters of Rox-Methyl and Rox-Gluc in mouse plasma showed similar profiles to that of Rox and both compounds showed similar biological activities. Of note, Rox-Methyl showed shorter half-life than Rox-Gluc in vivo, implying the easy escape from anti-doping screen. These results demonstrate that the global metabolomics method introduced in this study will contribute to the identification and detection of HIF-analog doping. Roxadustat, hypoxia-inducing transcription factor, UHPLC-QTOF/MS, global metabolomics, doping © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of Biochemistry. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Biochemistry Oxford University Press

Retracted: Detection of novel metabolite for Roxadustat doping by global metabolomics

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of Biochemistry.
ISSN
0021-924X
eISSN
1756-2651
D.O.I.
10.1093/jb/mvy028
Publisher site
See Article on Publisher Site

Abstract

Summary Roxadustat (FG-4592, Rox) is a stabilizer for hypoxia-inducible transcription factors (HIFs), which induce production of the erythroid growth factor erythropoietin, and has been listed by the World Anti-Doping Agency as a prohibited substance for athletes since 2011. Although the detection technologies for Rox and its glucuronide-conjugated metabolite (Rox-Gluc) have been developed exploiting triple quadrupole mass spectrometry (MS/MS), the production of metabolites from Rox in the human body remains to be clarified. Here, we established a protocol for the detection of unknown metabolites in plasma and urine samples from Rox-doping mice by global metabolomics using an ultra high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). We identified methylated Rox (Rox-Methyl), a novel metabolite, and Rox-Gluc in mouse urine by principal component analysis and orthogonal partial least squares discriminant analysis based on detected features by UHPLC-QTOF/MS analysis. The estimated pharmacokinetic parameters of Rox-Methyl and Rox-Gluc in mouse plasma showed similar profiles to that of Rox and both compounds showed similar biological activities. Of note, Rox-Methyl showed shorter half-life than Rox-Gluc in vivo, implying the easy escape from anti-doping screen. These results demonstrate that the global metabolomics method introduced in this study will contribute to the identification and detection of HIF-analog doping. Roxadustat, hypoxia-inducing transcription factor, UHPLC-QTOF/MS, global metabolomics, doping © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of Biochemistry. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

Journal

The Journal of BiochemistryOxford University Press

Published: Feb 9, 2018

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