Effects of methandienone on the performance and body composition of men undergoing athletic training
The 17-epimer was found in the urines after the intake of both mentioned anabolic-androgenic steroids. In the case of MT administration, the metabolite 11 was also described earlier, but found with shorter detection times than the 17α-methyl analogs 19 and 20 [38]. After the intake of MD, this was also found earlier, but with a problem in separation of the four diastereomers [15].
5. Urine Sample Preparation
Laboratories mainly screen for the parent compound itself (18) and two reduced derivatives (3α5α-THMT, 19; 3α5β-THMT, 20). The metabolites of both substances are frequently monitored by gas chromatography-mass spectrometry after hydrolysis of the glycosidic bond of glucuronides as aglycons [22,23]. Many metabolites related to the intake of metandienone are reported in the literature, and a number of these have been known for decades. These are generated by both phase I and phase II drug metabolizing enzymes.
The detection and structure identification of the above-mentioned substances in the urine samples help to gain further insights into human metabolism of metandienone and 17α-methyltestosterone. Due to the similarity of other anabolic androgenic steroids to the investigated compounds, it is probable that other metabolites with related structures may be found in further 17α-methyl steroids. Finally, the results may support the fight against doping by introducing new analytes for screening in anti-doping analysis. As is common in several doping control laboratories, glucuronidated metabolites are enzymatically cleaved and determined as their aglycons together with their analogs that are excreted as unconjugated compounds. Due to the low abundance of some of the target analytes, GC-QQQ-MS in MRM mode is considered as a better-suited technique for Buy USA steroids metabolite detection after optimization of the ion transitions.
The discovery of such new metabolites may help in extending the time of detection after the intake of metandienone (12) or methyltestosterone (18), which would be a considerable contribution to the fight against doping, as cheating may be traced back over a longer period. Additionally, such findings may help to further elucidate the metabolism of synthetic steroids and therefore improve the understanding of human biotransformation. After cooling to 0 °C, Nysted reagent (20%) was diluted with absolute tetrahydrofurane (THF abs.), and titanium tetrachloride was added dropwise.
- Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis.
- Urine samples from the administration trials were analyzed with a GC-QTOF-MS and GC-QQQ-MS after per-TMS derivatization.
- The method was adapted from Kratena et al. [33] but started with regularly C13β-CH3 configured androstanes in contrast to the ent-configurated (C13α-CH3) androstanes used by Kratena et al.
- The crude substance was dissolved in dichloromethane, and potassium hydrogen carbonate and meta-chloroperoxybenzoic acid were added.
Side Effects
1H and 13C NMR spectral data of 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol (8) and 17α-hydroxymethyl-17β-methyl-18-nor-5α-androst-13-en-3α-ol (8a). Metandienone is an anabolic steroid indicated for appetite stimulation in patients with anorexia. Generation of 17α-hydroxymethyl-17β-methyl-18-norandrosta-1,4,13-trien-3-one is generated from the intermediate 17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one by CYP3A4 catalyzed hydroxylation [20], while CYP21A1-catalyzed hydroxylation leads to the formation of a 17β-hydroxymethyl-17α-methyl analog [20]. Urine samples from the administration trials were analyzed with a GC-QTOF-MS and GC-QQQ-MS after per-TMS derivatization. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of the School of Pharmaceutical Science and Technology, Tianjin University (date of approval 9 December 2020). There are many known cases of doping in sports with metandienone by professional athletes.
Phase I reactions include the introduction of a double bond at position 6, the reduction of double bonds in the A-ring, the reduction of the 3-oxo group, hydroxylations in positions 6, 11, 12, 16, or 18, epimerization in position 17, and rearrangement of the D-ring [8,9,10,11,12,13,14,15]. With respect to phase II reactions, both glucuronidation and sulfonation have been reported [16,17]. In recent years, new investigations on long-term metabolites of MD (12) identified further metabolites with 17β-hydroxymethyl-17α-methyl-13-ene structure [18,19,20,21]. Anti-doping laboratories mostly target the parent compound (12), 6-OH-metandienone (13), epi-metandienone (14), epi-metendiol (15), nor-epi-metendiol (16), and 20βOH-nor-metandienone (17) [18,22,23]. Aberrantly, only 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol (8) was confirmed in the p.a. The stereochemistry at C17 is the opposite of the currently monitored long-term metabolite of MD and also to 17β-hydroxymethyl-17α-methyl-18-nor-androsta-4,13-dien-3-one, which was detected earlier after administration of MT [38].
