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Int J Mol Sci. 2016 Oct; 17(10): 1676.
Published online 2016 Oct 3. doi: 10.3390/ijms17101676
PMCID: PMC5085709
PMID: 27706103
In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011
Lore Geldof,* Koen Deventer, Kris Roels, Eva Tudela, and Peter Van Eenoo
Chang Won Choi, Academic Editor
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Abstract
SR9009 and SR9011 are attractive as performance-enhancing substances due to their REV-ERB agonist effects and thus circadian rhythm modulation activity. Although no pharmaceutical preparations are available yet, illicit use of SR9009 and SR9011 for doping purposes can be anticipated, especially since SR9009 is marketed in illicit products. Therefore, the aim was to identify potential diagnostic metabolites via in vitro metabolic studies to ensure effective (doping) control. The presence of SR9009 could be demonstrated in a black market product purchased over the Internet. Via human liver microsomal metabolic assays, eight metabolites were detected for SR9009 and fourteen metabolites for SR9011 by liquid chromatography–high resolution mass spectrometry (LC–HRMS). Structure elucidation was performed for all metabolites by LC–HRMS product ion scans in both positive and negative ionization mode. Retrospective data analysis was applied to 1511 doping control samples previously analyzed by a full-scan LC–HRMS screening method to verify the presence of SR9009, SR9011 and their metabolites. So far, the presence of neither the parent compound nor the metabolites could be detected in routine urine samples. However, to further discourage use of these potentially harmful compounds, incorporation of SR9009 and SR9011 into screening methods is highly recommended.
Keywords: REV-ERB agonists, SR9009, SR9011, phase I metabolism, in vitro studies, liquid chromatography–high resolution mass spectrometry (LC–HRMS), doping agents
Published online 2016 Oct 3. doi: 10.3390/ijms17101676
PMCID: PMC5085709
PMID: 27706103
In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011
Lore Geldof,* Koen Deventer, Kris Roels, Eva Tudela, and Peter Van Eenoo
Chang Won Choi, Academic Editor
Go to:
Abstract
SR9009 and SR9011 are attractive as performance-enhancing substances due to their REV-ERB agonist effects and thus circadian rhythm modulation activity. Although no pharmaceutical preparations are available yet, illicit use of SR9009 and SR9011 for doping purposes can be anticipated, especially since SR9009 is marketed in illicit products. Therefore, the aim was to identify potential diagnostic metabolites via in vitro metabolic studies to ensure effective (doping) control. The presence of SR9009 could be demonstrated in a black market product purchased over the Internet. Via human liver microsomal metabolic assays, eight metabolites were detected for SR9009 and fourteen metabolites for SR9011 by liquid chromatography–high resolution mass spectrometry (LC–HRMS). Structure elucidation was performed for all metabolites by LC–HRMS product ion scans in both positive and negative ionization mode. Retrospective data analysis was applied to 1511 doping control samples previously analyzed by a full-scan LC–HRMS screening method to verify the presence of SR9009, SR9011 and their metabolites. So far, the presence of neither the parent compound nor the metabolites could be detected in routine urine samples. However, to further discourage use of these potentially harmful compounds, incorporation of SR9009 and SR9011 into screening methods is highly recommended.
Keywords: REV-ERB agonists, SR9009, SR9011, phase I metabolism, in vitro studies, liquid chromatography–high resolution mass spectrometry (LC–HRMS), doping agents