Synthesis of a human long-term oxymetholone metabolite

Area of Science:

• * Analytical Chemistry
• * Organic Synthesis
• * Pharmacology

Background:

• * Oxymetholone (OXM) is an anabolic-androgenic steroid used therapeutically and illicitly.
• * Identifying and synthesizing its long-term metabolites is crucial for doping control and understanding its pharmacokinetics.
• * Previous studies identified a metabolite (OXM-M2) via GC-MS/MS, necessitating its chemical synthesis for further validation.

Purpose of the Study:

• * To develop efficient synthetic routes for oxymetholone metabolites.
• * To synthesize and confirm the structure of a specific long-term oxymetholone metabolite (OXM-M2).
• * To provide reference standards for doping analysis.

Main Methods:

• * Synthesis of oxymetholone metabolite (OXM-M2) from commercially available precursors.
• * Development of two distinct synthetic pathways.
• * Structure elucidation using Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) and Single Crystal X-ray Diffraction.

Main Results:

• * Two efficient synthetic routes were established for accessing C-17 epimers of tentative oxymetholone metabolites.
• * The in vivo metabolite, 17β-hydroxymethyl-2α,17α-methyl-18-norandrost-13-en-3-one, was successfully synthesized.
• * Single crystal X-ray diffraction confirmed the identity and molecular configuration of the synthesized metabolite.

Conclusions:

• * The successful synthesis and structural confirmation of the oxymetholone metabolite provide a crucial reference standard.
• * This work aids in the accurate detection and identification of oxymetholone use in anti-doping efforts.
• * The developed synthetic methodologies can be applied to the synthesis of related steroid metabolites.