Comparison of urinary excretion patterns among exposures to cosmetic preservative, herbicide, and nootropic stimulant in anti-doping analysis – PubMed Black Hawk Supplements

Abstract

Doping with meclofenoxate, a nootropic stimulant prohibited in-competition by the World Anti-Doping Agency (WADA), is identified through the primary marker of urinary 4-chlorophenoxyacetic acid (4-CPA). However, the presence of 4-CPA can also arise from permissible sources. This study ventured into comparing urinary excretion patterns among exposures to permitted chemicals (chlorphenesin and 4-CPA) and the banned stimulant (meclofenoxate) and interpreting the analytical findings according to the reporting requirements. A validated method, utilising direct injection and ultra-performance liquid chromatography-tandem mass spectrometry, was employed for urine analysis. In the first experiment, participants applied chlorphenesin-containing cosmetics with varied functions, dosages, frequencies, and application sites. Sunscreen usage led to significantly higher urinary 4-CPA concentrations (up to 1049 ng/mL) as compared to others, highlighting the impact of cosmetic formulation composition for chlorphenesin delivery. The diagnostic marker for preservative exposure included 3-(4-chlorophenoxy)-2-hydroxypropanoic acid (4-CPP) and chlorphenesin and its conjugated metabolites, with 4-CPP reaching higher concentrations (C_max of 903-7629 ng/mL) and for a longer period, up to 7-14 days. In the second experiment involving meclofenoxate supplement administration, urinary C_max levels of 4-CPA were observed between 36,287 and 39,769 ng/mL at 3-10 h post-dosing, with the parent meclofenoxate undetected in all participants’ samples. The third experiment, focused on occupational herbicide exposure in agricultural environments, detected minimal 4-CPA (< 10 ng/mL) in urine. WADA's current guidance for meclofenoxate aligns with reporting correct analytical results. Investigations, such as the experimental approach herein, offer valuable evidence addressing accuracy concerns in anti-doping tests, contributing insights for future amendments.

Keywords: 4-Chlorophenoxyacetic acid; Centrophenoxine; Chlorphenesin; Meclofenoxate; Sports drug testing; World Anti-Doping Agency.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.