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Metabolic profiles of MK-3984 (SARM) in zebrafish using Ultra High Performance liquid chromatography Q Extractive HF Hybrid Quadrupole Orbitrap mass spectrometry (UPLC-QE-HF-MS) for doping control
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DOI：10.1039/D6AN00421K.png)
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Abstract
En 中文
In this study; the metabolic profiles of MK-3984; a selective androgen receptor modulator (SARM) targeting muscle and bone tissues; were comprehensively investigated for the first time using Quadrupole Orbitrap LC-MS/MS in a zebrafish model. The analysis revealed 82 metabolites (M1-M82) and identified 12 distinct metabolic pathways.Phase I metabolism was predominantly characterized by reductive defluorination; while phase II metabolism primarily involved cysteinylation and sulfation. Notably; this study first reported the characteristic neutral losses (87 and 129 Da) associated with cysteinylated and N-acetylated-cysteinylated metabolites in negative ion mode. Three key metabolites-M1 (reductive defluorinated metabolite); M28 (reductive defluorinated; monohydroxylated and sulfated metabolite); and M55 (reductive defluorinated; monohydroxylated and cysteinylated metabolite) were identified as potential biomarkers for monitoring MK-3984 abuse. These findings provide valuable insights into the metabolic fate of MK-3984 and establish a foundation for its detection in anti-doping controls.
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