Comprehensive plasma-screening for known and unknown substances in doping controls.

Area of Science:

• Analytical Chemistry
• Biochemistry
• Forensic Science

Background:

• Doping analysis faces challenges from new, untested performance-enhancing drugs.
• Classical targeted methods are insufficient for detecting novel or unknown xenobiotics.
• A comprehensive screening procedure is needed to complement existing doping controls.

Purpose of the Study:

• To develop a new analytical strategy for identifying known and unknown doping agents in plasma.
• To circumvent the limitations of targeted doping analysis with a more comprehensive approach.
• To enhance the detection capabilities for illicit substances in sports.

Main Methods:

• Utilized a small plasma volume (50 microL) for analysis.
• Employed liquid chromatography coupled with high resolution/high accuracy orbitrap mass spectrometry.
• Implemented a novel hyphenated mass spectrometry technique with higher collision energy dissociation (HCD) fragmentation without precursor ion selection.

Main Results:

• Successfully identified numerous WADA-prohibited compounds from various classes.
• Achieved low ng/mL detection limits for model compounds.
• Validated method for specificity, selectivity, limit of detection, precision, robustness, linearity, ion suppression, and recovery.
• Demonstrated retrospective identification of unknown substances from HCD mass spectra.

Conclusions:

• The developed method offers a sensitive and specific approach for doping control.
• It enables simultaneous screening for known drugs and identification of unknown compounds.
• This strategy enhances anti-doping capabilities by addressing the challenge of novel performance-enhancing substances.