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Mario Thevis's Lab

Featured research (3)

Isopropylnorsynephrine (isopropyloctopamine, deterenol, 4‐(1‐hydroxy‐2‐(isopropylamino)ethyl)phenol), a beta‐selective and direct‐acting adrenergic agonist, has been reported in the past as declared as well as non‐declared ingredient of dietary supplements. The proven biological activity and the structural similarity of isopropylnorsynephrine to substances classified as prohibited compounds according to the World Anti‐Doping Agency's (WADA's) regulations could necessitate the inclusion of this sympathomimetic amine into routine doping control analytical assays. Therefore, information on urinary metabolites is desirable in order to allow for an efficient implementation of target compounds into existing multi‐analyte testing procedures, enabling the unequivocal identification of the administration of isopropylnorsynephrine by an athlete. In a pilot study setting, urine samples were collected prior to and after the oral application of ca. 8.7 mg of isopropylnorsynephrine, which were subjected to liquid chromatography‐high resolution/high accuracy (tandem) mass spectrometry. The intact drug, hydroxylated and/or glucurono‐ or sulfo‐conjugated isopropylnorsynephrine were detected up to 48 h post‐administration, with isopropylnorsynephrine sulfate representing the most abundant urinary target analyte. No relevant amounts of the dealkylation product (octopamine) were observed, indicating that merely moderate adaptations of existing test methods (or data evaluation strategies) are required to include isporpoylnorsynephrine in antidoping analytics, if required.
The possibility of nutritional supplement contamination with minute amounts of the selective androgen receptor modulator (SARM) ostarine has become a major concern for athletes and result managing authorities. In case of an adverse analytical finding (AAF), affected athletes need to provide conclusive information, demonstrating that the test result originates from a contamination scenario rather than doping. The aim of this research project was to study the elimination profiles of microdosed ostarine and characterize the time‐dependent urinary excretion of the drug and selected metabolites. Single‐ and multi‐dose administration studies with 1, 10, and 50 μg of ostarine were conducted, and collected urine samples were analyzed by LC‐MS/MS following solid‐phase extraction or enzymatic hydrolysis combined with liquid‐liquid extraction. In the post‐administration samples, both the maximum urine concentrations/abundance ratios and detection times of ostarine and its phase‐I and phase‐II metabolites were found to correlate with the administered drug dose. With regard to the observed maximum levels of ostarine, the time points of peak urinary concentrations/abundance ratios, and detection windows, a high inter‐individual variation was observed. However, the study demonstrated that a single oral dose of as little as 1 μg can be detected for up to 9 (5) days by monitoring ostarine (glucuronide), and hydroxylated metabolites (especially M1a) appear to offer a considerably shorter detection window. The obtained data on ostarine (metabolite) detection times and urinary concentrations following different administration schemes support the interpretation of AAFs, in particular when scenarios of proven supplement contamination are discussed and supplement administration protocols exist.
RATIONALE Exhaled breath (EB) has been demonstrated to be a promising alternative matrix in sports drug testing due to its non‐invasive and non‐intrusive nature compared with urine and blood collection protocols. In this study, a pilot‐test system was employed to create drug‐containing aerosols simulating EB in support of the analytical characterization of EB sampling procedures, and the used analytical method was extended to include a broad spectrum of prohibited substances. METHODS Artificial and authentic EB samples were collected using sampling devices containing an electret filter, and doping agents were detected by means of liquid chromatography and tandem mass spectrometry with unispray ionization. The analytical approach was characterized with regard to specificity, limits of detection, carry‐over, recovery and matrix effects, and the potential applicability to routine doping controls was shown using authentic EB samples collected after single oral dose applications of glucocorticoids and stimulants. RESULTS The analytical method was found to be specific for a total of 49 model substances relevant in sports drug testing, with detection limits ranging from 1 to 500 pg per cartridge. Both ion suppression (‐62%) and ion enhancement (+301%) effects were observed, and all model compounds applied to EB sampling devices were still detected after 28 days of storage at room temperature. Authentic EB samples collected after the oral administration of 10 mg of prednisolone resulted in prednisolone findings in specimens obtained from 3 out of 6 participants up to 2 h. In octodrine, dimethylamylamine (DMAA), and isopropylnorsynephrine post‐administration EB samples, the drugs were detected over a period of 48, 50, and 8 h, respectively. CONCLUSIONS With the analytical approach developed within this study, the identification of a broad spectrum of prohibited doping agents in EB samples was accomplished. Application studies and stability tests provided information to characterize EB as a potential matrix in sports drug testing.

Lab head

Members (4)

Oliver Krug
  • Deutsche Sporthochschule Köln
Luisa Euler
  • Deutsche Sporthochschule Köln
Sam Thilmany
  • Deutsche Sporthochschule Köln
Sophia Krombholz
  • Deutsche Sporthochschule Köln
Katja Walpurgis
Katja Walpurgis
  • Not confirmed yet
Thomas Pieper
Thomas Pieper
  • Not confirmed yet
Felicitas Wagener
Felicitas Wagener
  • Not confirmed yet
Insa Peters
Insa Peters
  • Not confirmed yet
Mario Thevis
Mario Thevis
  • Not confirmed yet
Andreas Thomas
Andreas Thomas
  • Not confirmed yet
Nana Ueffing
Nana Ueffing
  • Not confirmed yet
Mario Thevis
Mario Thevis
  • Not confirmed yet