Terbutaline sulfoconjugate: characterization and urinary excretion monitored by LC/ESI-MS/MS

Area of Science:

• Pharmacology
• Analytical Chemistry
• Sports Science

Background:

• Terbutaline, a beta(2)-adrenergic agonist, is used for obstructive pulmonary diseases.
• Beta(2)-agonists are prohibited in sports by the World Anti-doping Agency (WADA).
• Current doping control involves detecting terbutaline metabolites after hydrolysis.

Purpose of the Study:

• To synthesize and characterize the mono-sulfoconjugated phase-II metabolite of terbutaline.
• To verify the structure of the terbutaline metabolite.
• To improve doping control procedures for terbutaline detection.

Main Methods:

• Synthesis of mono-sulfoconjugated terbutaline metabolite.
• (1)H-nuclear magnetic resonance spectrometry for structural characterization.
• High resolution/high accuracy Orbitrap mass spectrometry for metabolite identification.
• Excretion study in urine samples after terbutaline administration.

Main Results:

• The phenolic esterified compound (phenolic sulfate) of terbutaline was synthesized and structurally verified.
• The benzylic esterified compound was synthesized but not detected in urine.
• Phenolic sulfate was detected in urine for 2–4 days post-administration.
• Unchanged terbutaline was detected for 4–5 days post-administration.
• No glucuronidated or polysulfated metabolites were found.

Conclusions:

• The phenolic sulfate is the primary phase-II metabolite of terbutaline.
• This verified metabolite is essential for accurate doping control.
• Incorporating metabolite measurement can expedite sample preparation in anti-doping screening.