Several recent studies have shown evidence of some nutritional supplements containing prohibited anabolic androgenic steroids, so-called prohormones, which were not declared on the label. Therefore, a broad-based investigation of the international nutritional supplement market was initiated to clarify the extent of this problem. From October 2000 until November 2001, 634 non-hormonal nutritional supplements were purchased in 13 countries from 215 different suppliers. Most supplements were bought in shops in the respective countries (578 samples = 91.2 %) and on the internet (52 samples = 8.2 %). 289 supplements were from prohormone-selling companies and 345 supplements came from companies which do not offer prohormones. After isolation from the supplement matrix 11 different anabolic androgenic steroids, mainly prohormones of testosterone and nandrolone, were analysed by gas-chromatography/mass spectrometry. Out of the 634 samples analysed 94 (14.8 %) contained anabolic androgenic steroids not declared on the label ("positive supplements"). We could not obtain reliable data for 66 samples (10.4 %) due to matrix effects. In relation to the total number of products purchased per country, most of the positive supplements were bought in the Netherlands (25.8 %), in Austria (22.7 %), in the UK (18.8 %) and the USA (18.8 %). According to the label, all positive supplements were from companies located in only five countries: the USA, the Netherlands, the UK, Italy and Germany. 21.1 % of the nutritional supplements from prohormone-selling companies contained anabolic androgenic steroids, whereas 9.6 % of the supplements from companies not selling prohormones were positive. The positive supplements showed anabolic androgenic steroid concentrations of 0.01 micro g/g up to 190 micro g/g. The administration of supplements containing nandrolone prohormones adding up to a total uptake of more than 1 micro g resulted in positive doping results for norandrosterone for several hours.
[ Abstract IIn the context of house searches in Germany, numerous drugs were confiscated and subjected to chemical analysis, including anabolic agents such as various anabolic-androgenic steroids (stanozolol, testosterone derivatives, trenbolone esters, etc.) and clenbuterol, as well as agents with anti-estrogenic activity (tamoxifen, clomiphene), drugs stimulating virility (sildenafil, tadalafil), and unlabeled plastic bags. Liquid chromatographytandem mass spectrometry, gas chromatography-mass spectrometry with nitrogen-phosphorus specific detection, gel electrophoresis, and immunological tests were employed to test for the effective content of 70 products. In 18 cases (25.7%), the declared ingredients differed from the actual content, in particular concerning anabolic-androgenic steroids. Nandrolone and trenbolone esters, for instance, were frequently substituted or complemented by various testosterone derivatives, and several testosterone depot formulations originally composed of four different esters were found to contain fewer or wrong components. Except for those drugs supposedly originating from so-called underground labs, fake packings were hardly or not distinguishable from original boxes by visual inspection.resulting side effects such as the reduction in vessel-protective HDL cholesterol, early atherosclerosis, prothrombotic effects, liver tumors, and others were observed in numerous case studies with and without lethal consequences (2-11).During the last 10 years, numerous products that supposedly support athletic performance and muscle growth were obtained from different commercial sources (e.g., via Internet order) but also confiscated in house searches. Several of those were identified as counterfeit substances. In the present report, we describe the analysis of 70 products collected from three different individuals under suspicion for dealing with prescription drugs and illegal compounds. As packaging and labels were not differentiable from original counterparts, aliquots of all drugs were subjected to liquid chromatography-tandem mass spectrometry (LC-MS-MS) or gas chromatography-mass spectrometry with nitrogen-phosphorus specific detection (GC-MS-NPD) in order to determine whether these drugs were authentic or fake products. In addition, unlabeled plastic bags were analyzed for their content using MS approaches with and without chemical derivatization.
The elucidation of the metabolism of new therapeutics is a major task for pharmaceutical companies and of great interest for drug testing laboratories. The latter in particular need to determine the presence or absence of drugs or their metabolic products in urine to test for a misuse of these compounds. Commonly, in vitro or animal models are used to mimic the human metabolism and produce potential targets in amounts allowing for method development. An alternative route based on electrochemical reactions of drugs was reported to allow for the generation of selected metabolites. The utility of this approach for doping control purposes was demonstrated with a novel class of anabolic agents termed selective androgen receptor modulators (SARMs). An arylpropionamide- derived drug candidate was subjected to electrochemical "metabolism" and a major phase-I- metabolite, resulting from the elimination of a substituted phenol residue as identified in in vitro experiments, was generated and characterised using liquid chromatography/nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. The metabolite was included in routine doping control procedures based on liquid chromatography/tandem mass spectrometry and has served as a reference compound for 5000 doping control specimens.
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 physiology or due to various species-specific differences using animal models. A more recently established technology for simulating human physiology is the "organ-on-a-chip" principle. In a multichannel microfluidic cell culture chip, 3-dimensional tissue spheroids, which can constitute artificial and interconnected microscale organs, imitate principles of the human physiology. The objective of this study was to determine if the technology is suitable to adequately predict metabolic profiles of prohibited substances in sport. As model compounds, the frequently misused anabolic steroids, stanozolol and dehydrochloromethyltestosterone (DHCMT) were subjected to human liver spheroids in microfluidic cell culture chips. The metabolite patterns produced and circulating in the chip media were then assessed by LC-HRMS/(MS) at different time points of up to 14 days of incubation at 37 C. The overall profile of observed glucurono-conjugated stanozolol metabolites excellently matched the commonly found urinary pattern of metabolites, including 3 0 OHstanozolol-glucuronide and stanozolol-N-glucuronides. Similarly, but to a lower extent, the DHCMT metabolic profile was in agreement with phase-I and phase-II biotransformation products regularly seen in postadministration urine specimens. In conclusion, this pilot study indicates that the "organ-on-a-chip" technology provides a high degree of conformity with traditional human oral administration studies, providing a promising approach for metabolic profiling in sports drug testing.Organ-on-a-chip: Proof-of-concept study in sports drug testing Christian Görgens and Anja Patricia Ramme contributed equally.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.