Mario Thevis's research while affiliated with Deutsche Sporthochschule Köln and other places
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Publications (581)
2‐(Dimethylamino)ethan‐1‐ol (Deanol) is a widely produced chemical used by both industry and consumers in a variety of applications. Meclofenoxate, a stimulant classified on the World Anti‐Doping Agency Prohibited List, metabolizes into deanol and, presumably, its main metabolite deanol‐ N ‐oxide. Hence, using liquid chromatography–tandem mass spec...
Because of its influence on carbohydrate metabolism and, at the same time, anti-catabolic effects, the misuse of the peptide hormone insulin and its synthetic analogs is prohibited in sports at all times according to the regulations of the World Anti-Doping Agency (WADA). The biological effects of insulin and its analogs are mediated through bindin...
Capromorelin is a growth hormone secretagogue. Despite promising results to alleviate muscle-wasting in the elderly, it has not advanced further in human development. Subsequent studies demonstrated capromorelin's ability to increase food intake in animals, leading to approval in the United States and Europe as an appetite stimulant for cats (Elura...
Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was...
Higenamine is prohibited in sports as a β2 -agonist by the World Anti-Doping Agency. As a key component of a great variety of plants, including the Annonaceae family, one aim of this research project was to evaluate whether the ingestion of Annona fruit could lead to higenamine adverse analytical findings. Single-dose administration studies includi...
Among anabolic agents, selective androgen receptor modulators (SARMs) represent a new class of potential drugs that can exhibit anabolic effects on muscle and bone with reduced side effects due to a tissue-selective mode of action. Besides possible medical applications, SARMs are used as performance-enhancing agents in sports. Therefore, they are p...
A recent study addressed the possibility of unintentional ingestion of clomiphene through residues in chicken eggs. The method developed here helped distinguish between microdose intake of ( E / Z )‐clomiphene citrate and consumption of clomiphene‐containing eggs by the urinary pattern of four mono‐hydroxylated clomiphene metabolites. However, rean...
The identification of metabolites allows for the expansion of possible targets for anti-doping analysis. Especially for novel substances such as selective androgen receptor modulators (SARMs), information on metabolic fate is scarce. Novel approaches such as the organ on a chip technology may provide a metabolic profile that resembles human in vivo...
Hormonal contraception is a widely adopted method for preventing unintended pregnancies, giving women effective control over their reproductiveness. However, a concerning association has been observed between hormonal contraception and an increased risk of mental illness, particularly depression. The evidence for this association primarily relies o...
LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control....
Background:
Studies have revealed that vancomycin soaking of the anterior cruciate ligament (ACL) graft can drastically reduce the incidence of postoperative infections after ACL reconstruction. However, it remains unknown whether the chondrotoxic threshold of vancomycin in synovial fluid is exceeded during this process. Several studies investigat...
Depressionen sind laut der Weltgesundheitsorganisation (WHO) eine weit verbreitete Erkrankung mit einer weltweiten Prävalenz von 3,8 Prozent. Über die Risikofaktoren für die Entwicklung einer Depression ist wenig bekannt. Es scheint jedoch klar zu sein, dass sie multifaktoriell bedingt ist und ein komplexes Zusammenspiel von sozialen, psychischen u...
Currently, primarily urine, whole blood, and serum samples are analyzed for doping-relevant substances in professional sports, but recently dried blood spots (DBS) have been introduced as complementary matrix, offering advantageous features e.g. the minimally invasive sampling procedure. In order to cope with the increased application of DBS, a com...
Across species, skeletal muscle mass is negatively regulated by the TGF-β cytokine myostatin (MSTN). Inhibitors of this growth factor and its signaling pathways are therefore not only promising therapeutics for muscular diseases but also potential performance-enhancing agents in sports. Within this study, protein precipitation and liquid chromatogr...
The numbers of vitamin D inadequacies has reportedly increased in the general population, especially in the Northern hemisphere. However, routine measurement of 25(OH) vitamin D is usually associated with a substantial effort due to the requirement of a venous blood sample taken by medical professionals. Thus, the objective of this work is to devel...
Steroid hormone use is still popular among athletes; according to the 2021 testing figures of the World Anti-Doping Agency (WADA), almost 900 samples tested positive for steroids. Steroids are also widely used for medical reasons, e.g., hormonal contraception, hormone replacement therapy, or cancer treatment.
In addition to the desired therapeutic...
Along with the recent acknowledgement of the World Anti‐Doping Agency to use dried blood spot (DBS) samples for routine doping control purposes, there have been propositions to use DBS as a matrix that allows regular proactive remotely supervised self‐sampling, providing potential longitudinal monitoring of an athlete’s exposure to doping agents. H...
The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method.
Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4...
The anabolic properties of 11‐hydroxyandrostenedione (OHA4) and its physiologically active metabolites 11‐ketotestosterone (KT) and 11‐ketodihydrotestosterone (KDHT) have been discussed in several recent publications. Especially KT has become readily available via internet‐based providers. No doping control methods for the detection of KT or KDHT e...
Aims/hypothesis
Post-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes...
Test methods in anti‐doping, most of which rely on the most modern mass spectrometric instrumentation, undergo continuous optimization in order to accommodate growing demands as to comprehensiveness, sensitivity, retrospectivity, cost‐effectiveness, turnaround times, etc. While developing and improving analytical approaches is vital for appropriate...
The detection of testosterone intake is facilitated by monitoring the urinary steroid profile in the athlete biological passport. This technique can be used with confidence to identify target samples for isotope ratio mass spectrometry. Regrettably, most research has been performed on male subjects resulting in a method that does not account for fe...
Potential scenarios as to the origin of minute amounts of banned substances detected in doping control samples have been a much-discussed problem in anti-doping analysis in recent years. One such debated scenario has been the contamination of female athletes’ urine with ejaculate containing doping agents and/or their metabolites. The aim of this wo...
The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) tool kit constitutes one of today's most frequently used gene editing techniques. Editing of virtually any DNA sequence can be realised, due to the quickly progressing research into different Cas effectors and their ever-expanding range of targets. Moreover...
AICAr (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, commonly referred to as AICAR) is an adenosine monophosphate-activated protein kinase agonist previously investigated for its therapeutic potential which has been shown to improve exercise performance in laboratory animals. For this reason, the World Anti-Doping Agency prohibits the use of...
Myostatin propeptide is prohibited according to chapter S4 of the "WADA 2022 List of Prohibited Substances and Methods". So far, no approved myostatin-propeptide pharmaceuticals are available. Nevertheless, myostatin-propeptides can be bought on the black market for "research purposes". A study on black market myostatin propeptide products is prese...
Also in 2021/2022, considerable efforts were invested into advancing human sports drug testing programs, recognizing and taking into account existing as well as emerging challenges in anti‐doping, especially with regards to substances and methods of doping specified in the World Anti‐Doping Agency’s 2022 Prohibited List. In this edition of the annu...
Depression is a common disorder with a worldwide prevalence of 3.8 %, according to the World Health Organization (WHO). Little is known about the risk factors for the development of depression. However, it seems clear that it is multifactorial and requires a complex interaction of social, psychological, and biological factors. A possible influence...
In 2020, the confirmation of the non-endogenous origin of several pseudo-endogenous steroids by means of isotope ratio mass spectrometry (IRMS) was recommended by the World Anti-Doping Agency (WADA), in addition to previously established target analytes for IRMS in sports drug testing. To date, however, IRMS-based methods validated in accordance wi...
Bioactive peptides with a molecular mass between 2 and 10 kDa represent an important class of substances banned in elite sports, which has been recognized with an increasing number and variety of substances by anti-doping organizations. Also, the annually renewed list of prohibited substances of the World Anti-Doping Agency (WADA) explicitly mentio...
Situations of both, intentional as well as inadvertent or accidental doping, necessitate consideration in today’s doping controls, especially in the light of the substantial consequences that athletes are facing in case of so‐called adverse analytical findings. The aim of this study was to investigate, whether a transdermal uptake of doping substan...
For decades, blood testing has been an integral part of routine doping controls. The breadth of information contained in blood samples has become considerably more accessible for anti-doping purposes over the last 10 years through technological advancements regarding analytical instrumentation as well as enhanced sample collection systems. Particul...
Background
The development of analytical approaches to help reduce the risk of growth hormone (GH) doping is important to fair competition and the health of athletes. However, the reliable detection of GH use remains challenging. The identification of novel biomarkers of GH administration could lead to a better understanding of the physiological re...
RAD140 is a selective androgen receptor modulator which has been abused in sporting competitions. Its use is prohibited by the World Anti-Doping Agency (WADA) for athletes at all times. In addition to its illicit use, adverse analytical findings of RAD140 in doping control samples might result from other scenarios, e.g., the ingestion of contaminat...
RATIONALE
The synthetic β-adrenoreceptor agonist zilpaterol is legitimately used as an animal feed supplement in selected countries due to its known effects on lipolysis and protein biosynthesis. These pharmacological characteristics of zilpaterol have contributed to its classification as doping agent in sport by the World Anti-Doping Agency. Howev...
Dried blood spot (DBS) testing allows fast, easy, and minimally invasive collection of microvolumes of blood. In an anti‐doping context, DBS testing has particular relevance for substances prohibited in‐competition only such as ephedrine, which is currently detected by urine analysis, since DBS can add information about the blood drug concentration...
Rationale:
The anabolic steroid 5α-androst-2-en-17-one (2EN) is sold as a prohormone and has been investigated regarding its potential as steroidal aromatase inhibitor. The administration of 2EN was detected in a doping control sample in 2015, and investigations into its metabolism allowed for the identification and characterization of three urina...
Aim: To compare endocrine and metabolic counterregulation to postprandial hypoglycemia in patients with postbariatric hypoglycemia (PBH) after gastric bypass (GB) vs. surgical and non-surgical controls.
Methods: Thirty-two adults (age 42.9±12.8 years, 13% male, BMI 28.2±4.3kg/m2) of 4 matched groups (PBH patients, GB, sleeve gastrectomy [SG] and no...
Consumption of hemp products is continuously growing, with an expanding scope of applications. Suppliers operate through different distribution channels but the Internet is a major retail platform. Hemp products are prepared from cannabis plants and, therefore, might contain a variety of different natural cannabinoids. According to the regulations...
Analytics employed in modern doping controls are designed to cover an extensive range of rather diverse classes of substances, all of which are banned in sport according to the list of prohibited substances and methods of doping, resulting from their potential to be performance-enhancing and/or harmful to health. Many of these bioactive substances...
The anti-estrogen clomiphene is prohibited in sports at all times. Yet, adverse analytical findings (AAFs) have increased since 2011. This is possibly due to improved analytical sensitivity, but also contamination of food of animal origin needs to be taken into consideration as a potential source of drug exposure. For instance, studies with laying...
Studying the metabolism of prohibited substances is an essential element in anti-doping research in order to facilitate and improve detectability. Whilst pharmacokinetic studies on healthy volunteers are valuable, they are often difficult, not least due to safety reasons and ethical constraints, especially concerning peptidic substances, which must...
Rationale: Anti-SARS-CoV-2 antibody responses elicited by infection or vaccination vary among individuals and over time. Their knowledge is of particular importance in, amongst others, elite sport. Can dried blood spots serve as a minimally-invasive, low-cost, decentralized tool to monitor the quantitative antibody response and thus represent an al...
RATIONALE Exhaled Breath (EB) was found to be a promising matrix in the field of sports drug testing due to the non-invasive and non-intrusive sampling procedure, but significant interindividual variations regarding detected drug concentrations have been observed in previous studies. In order to investigate whether the detectability of doping agent...
Purpose
Synthetic cannabinoids (SCs), highly metabolized substances, are rarely found unmodified in urine samples. Urine screening relies on SC metabolite detection, requiring metabolism knowledge. Metabolism data can be acquired via in vitro assays, e.g., human hepatocytes, pooled human liver microsomes (pHLM), cytochrome P450 isoforms and a funga...
Rationale
An increasing number of adverse analytical findings (AAFs) in routine doping controls has been suspected and debated to presumably result from intimate contact with bodily fluids (including ejaculate), potentially facilitating the transfer of prohibited substances. More precisely, the possibility of prohibited drugs being present in ejacu...
Immunopurification of doping control samples is a mandatory necessity in EPO analysis during a Confirmation Procedure; moreover, it has become common practice to also immunopurify samples for the Initial Testing Procedure. Typically used materials (e.g. Stemcell purification plate, MAIIA purification kit) rely on anti-EPO antibodies for purificatio...
For decades, anabolic androgenic agents have represented the substance class most frequently observed in doping control samples. They comprise synthetic and pseudoendogenous anabolic androgenic steroids and other, mostly non-steroidal compounds with (presumed) positive effects on muscle mass and function. While exogenous substances can easily be de...
LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated...
Context
Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay.
Objective
Test the hypothesis that longitudinal profiling of hGH biom...
The Prohibited List of the World Anti-Doping Agency (WADA) defines the analytical framework for the anti-doping laboratories by introducing the substances and methods banned in sport context and which shall be incorporated into the analytical test menus in order to comply with the accreditation requirements and to ensure globally harmonized perform...
Most core areas of anti‐doping research exploit and rely on analytical chemistry, applied to studies aiming at further improving the test methods’ analytical sensitivity, the assays’ comprehensiveness, the interpretation of metabolic profiles and patterns, but also at facilitating the differentiation of natural/endogenous substances from structural...
The misuse of 2‐phenylethylamine (PEA) in sporting competitions is prohibited by the World Anti‐Doping Agency (WADA). As it is endogenously produced, a method is required to differentiate between naturally elevated levels of PEA and the illicit administration of the drug. In 2015, a sulfo‐conjugated metabolite (2‐(2‐hydroxyphenyl)acetamide sulfate...
Various substances classified by the World Anti-Doping Agency (WADA) as prohibited in sports feature one or more chiral centers. Amongst those, few analytes exist that are so-called threshold substances, for which also enantiomerically pure drugs are available. The commonly employed non-chiral analysis of these compounds does not allow for differen...
The testing strategy for the detection of testosterone (T) or T‐prohormones is based on the longitudinal evaluation of urinary steroid concentrations accompanied by subsequent isotope ratio mass spectrometry (IRMS)‐based confirmation of samples showing atypical concentrations or concentration ratios. In recent years, the IRMS methodology focussed m...
The hunger hormone ghrelin (G) is classified as prohibited substance in professional sport by the World Anti‐Doping Agency (WADA), due to its known growth hormone releasing properties. The endogenous bioactive peptide consists of 28 amino acids with a caprylic acid attached to serine at position 3. Within this study it was aimed to develop methods...
Similar to the general population, elite athletes are exposed to a complex set of environmental factors including chemicals, radiation, but also biological and physical stressors, which constitute an exposome that is, unlike for the general population, subjected to specific scrutiny for athletes due to applicable anti‐doping regulations and associa...
Probing for evidence of the administration of prohibited therapeutics, drugs and/or drug candidates as well as the use of methods of doping in doping control samples is a central assignment of anti-doping laboratories. In order to accomplish the desired analytical sensitivity, retrospectivity, and comprehensiveness, a considerable portion of anti-d...
A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher‐order system p...
Lately, the veterinary drug Emidonol® has been discussed as a possible scenario for inadvertent doping in sports. Emidonol® is approved for use in livestock breeding, exhibiting antihypoxic and weak sedative effects. The veterinary drug rapidly dissociates into meldonium, a substance prohibited in sports, and is excreted largely in its unchanged fo...
Rationale:
Chlorphenesin is an approved biocide frequently used in cosmetics, and its carbamate ester is an approved skeletal muscle relaxant in certain countries for the treatment of discomfort related to skeletal muscle trauma and inflammation. A major urinary metabolite is 4-chlorophenoxy acetic acid (4-CPA), also known as para-chlorophenoxyace...
Little information on the human metabolism and urinary elimination of hydrafinil (9‐fluorenol) exists. In order to support preventive anti‐doping activities concerning compounds such as hydrafinil, a pilot elimination study was conducted with three healthy male volunteers receiving a single oral dose of 50 mg of hydrafinil. Urine samples were colle...
The selective oestrogen receptor modulator (SERM) clomiphene is therapeutically used to induce ovulation. While prohibited as a doping agent in sports, it is frequently detected in sports drug testing urine samples. Few reports exist on clomiphene’s (illicit) use in the farming industry to increase the egg production rate of laying hens, which crea...
In order to detect the misuse of testosterone (T) or boldenone (Bo) in doping control analysis, the confirmation of atypical findings employing the determination of carbon isotope ratios (CIR) is mandatory for issuing adverse analytical findings. Elevated concentrations of T (or elevated T/epitestosterone ratios) may result from confounding factors...
In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). F...
In order to detect the misuse of testosterone (T), urinary steroid concentrations and concentration ratios are quantified and monitored in a longitudinal manner to enable the identification of samples exhibiting atypical test results. These suspicious samples are then forwarded to isotope ratio mass spectrometry (IRMS)–based methods for confirmatio...
The exogenous anabolic‐androgenic steroid (AAS) stanozolol stays one of the most detected substances in professional sports. Its detection is a fundamental part of doping analysis and the analysis of this steroid has been intensively investigated for a long time. This contribution to the detection of stanozolol doping describes for the first time t...
The human microsomal cytochrome P450 enzyme CYP46A1 plays a crucial role in cholesterol elimination from the brain. It performs a 24-hydroxylation of cholesterol and is of outstanding significance for memory and cognition. This study demonstrates the catalytic activity of human CYP46A1 towards an anabolic androgenic steroid, oral turinabol (dehydro...
For decades, the class of anabolic androgenic steroids has represented the most frequently detected doping agents in athletes’ urine samples. Roughly 50% of all adverse analytical findings per year can be attributed to anabolic androgenic steroids, of which about 2/3 are synthetic exogenous steroids, where a qualitative analytical approach is suffi...
The increasing importance to determine bioactive peptide hormones such as insulin, its synthetic analogs, and C-peptide in urine samples represents an analytical challenge. The physiological concentrations of insulin in urine are commonly found at sub-ng/mL levels and thus represent a complex analytical task. C-peptide concentrations, on the other...
Objective
To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).
Methods
Sixty-nine pwMS (...
Serological test methods to detect anti‐SARS‐CoV‐2 antibodies represent a major measure to manage the pandemic caused by the coronavirus disease 2019 (COVID‐19). In this communication, test results obtained from minimal‐invasively collected dried blood spot (DBS) specimens, which can be sampled ‘at home’ without the need of medically trained person...
![pseudoMS³ mass spectra of (A) norepinephrine ([M+H]⁺ = m/z...](publication/349113799/figure/fig3/AS:11431281179420988@1691188485529/pseudoMS-mass-spectra-of-A-norepinephrine-M-Hm-z-1701315207-B-hydroxylated_Q320.jpg)
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 su...
Capillary blood sampled as dried blood spot (DBS) has shown substantial potential as test matrix in sports drug testing in various different settings, enabling the analysis of numerous different drugs and/or their respective metabolites. In addition to established beneficial aspects of DBS specimens in general (such as e.g. the minimally invasive a...
Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-...
Analytical methods to determine the potential misuse of the ghrelin mimetics capromorelin (CP-424,391), macimorelin (macrilen, EP-01572), and tabimorelin (NN703) in sports were developed. Therefore, different extraction strategies, i.e. solid-phase extraction, protein precipitation, as well as a 'dilute-and-inject' approach, from urine and EDTA-pla...
Erythropoietin (EPO) is a hormone, which stimulates the production of red blood cells. Due to its performance enhancing effect, it is prohibited by the World Anti‐Doping Agency (WADA). In order to reduce the detection window of EPO‐doping, athletes have been applying low doses of recombinant EPO (e.g. < 10 IU/kg body weight, daily or every second d...