Search results for: Androstane 3a,17b diol Glucuronide(5a)
#34318592 2021/07/27 To Up
5Î±-reductase inhibitors: evaluation of their potential confounding effect on GC-C-IRMS doping analysis.5Î±-reductase inhibitors (5-ARIs) are considered by the World Anti-doping Agency as potential confounding factors in evaluating the athlete steroid profile, since they may interfere with the urinary excretion of several diagnostic compounds. We herein investigated 5Î±-reductase inhibitors from a different perspective, by verifying their influence on the carbon isotopic composition of 5Î±- and 5Î²- reduced testosterone and nandrolone metabolites. The GC-C-IRMS analysis was performed on a set of urine samples collected from three male Caucasian volunteers after the acute and chronic administration of finasteride in combination with the intake of 19-norandrostenedione, a nandrolone precursor. The excretion and the isotopic profile of androsterone (A), etiocholanolone (Etio) 5Î±-androstane-3Î±,17Î²-diol (5Î±Adiol), and 5Î²-androstane-3Î±,17Î²-diol (5Î²Adiol) were determined as well as those of 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Pregnanediol (PD) and pregnanetriol (PT) were also measured as endogenous reference compounds to define the individual endogenous isotopic profile. Our results confirmed the impact of finasteride, especially if chronically administered, on the enzymatic pathway of testosterone and nandrolone, and pointed out the influence of 5-ARIs on Î´ C values of the selected target compounds determined in the IRMS confirmation analysis.
Loredana Iannella, Cristiana Colamonici, Davide Curcio, Francesco BotrÃ¨, Xavier de la Torre
2637 related Products with: 5Î±-reductase inhibitors: evaluation of their potential confounding effect on GC-C-IRMS doping analysis.1 module3 modules 6 ml 6 inhibitors 15 ml 1 module 25 MG100 ul10 plates1 module
#34212529 2021/07/01 To Up
Effects of the administration of miconazole by different routes on the biomarkers of the "steroidal module" of the Athlete Biological Passport.This article reports the results obtained from the investigation of the influence of miconazole administration on the physiological fluctuation of the markers of the steroid profile included in the "steroidal module" of the Athlete Biological Passport. Urines collected from male Caucasian subjects before, during, and after either systemic (i.e., oral and buccal) or topical (i.e., dermal) treatment with miconazole were analyzed according to validated procedures based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) (to determine the markers of the steroid profile) or liquid chromatography coupled to MS/MS (LC-MS/MS) (to determine miconazole urinary levels). The results indicate that only after systemic administration, the markers of the steroid profile were significantly altered. After oral and buccal administration, we have registered (i) a significant increase of the 5Î±-androstane-3Î±,17Î²-diol/5Î²-androstane-3Î±,17Î²-diol ratio and (ii) a significant decrease of the concentration of androsterone, etiocholanolone, 5Î²-androstane-3Î±,17Î²-diol, and 5Î±-androstane-3Î±,17Î²-diol and of the androsterone/etiocholanolone, androsterone/testosterone, and 5Î±-androstane-3Î±,17Î²-diol/epitestosterone ratios. Limited effects were instead measured after dermal intake. Indeed, the levels of miconazole after systemic administration were in the range of 0.1-12.5Â Î¼g/ml, whereas after dermal administration were below the limit of quantification (50âng/ml). Significant alteration started to be registered at concentrations of miconazole higher than 0.5Â Î¼g/ml. These findings were primarily explained by the ability of miconazole in altering the kinetic/efficacy of deglucuronidation of the endogenous steroids by the enzyme Î²-glucuronidase during the sample preparation process. The increase of both incubation time and amount of Î²-glucuronidase was demonstrated to be effective countermeasures in the presence of miconazole to reduce the risk of uncorrected interpretation of the results.
Monica Mazzarino, Fabio ComunitÃ , Xavier de la Torre, Francesco Molaioni, Francesco BotrÃ¨
1904 related Products with: Effects of the administration of miconazole by different routes on the biomarkers of the "steroidal module" of the Athlete Biological Passport.100ul100.00 ul 100 G100 U200 units1100 500IU
#34051993 2021/05/06 To Up
A uniform sample preparation procedure for gas chromatography combustion isotope ratio mass spectrometry for all human doping control relevant anabolic steroids using online 2/3-dimensional liquid chromatography fraction collection.Androgenic anabolic steroids are the most misused substances in sports because of their performance-enhancing effects. Often synthetic analogues of endogenously present steroids are administered. To determine their endogenous or exogenous origin, Gas Chromatography Combustion Isotope Ratio Mass Spectrometry (GC-C-IRMS) is used in the field of doping control. Compounds subjected to IRMS analysis must be interference-free, with liquid chromatography fraction collection (HPLC-FC) being the crucial clean-up step. However, this clean-up is challenging, particularly for compounds present at low concentrations in samples with pronounced matrix effects. The compounds of interests for IRMS analyses in doping control are testosterone (T) and its main metabolites (androsterone, etiocholanolone, 5Î±-androstane-3Î±,17Î²-diol, 5Î²-androstane-3Î±,17Î²-diol), epitestosterone, 19-norandrosterone (19-NA), boldenone (B) and its main metabolite (BM), formestane (F) and 6Î±OH-androstenedione (6aOHADION). Currently, the available methods only deal with a selection of the above-mentioned compounds. Some of these compounds (e.g., 19-NA, B, BM, 6aOHADION) are present in very low concentrations, requiring an extensive and dedicated sample clean-up, and this makes it challenging to develop a universal clean-up procedure. Many of these methods require different and multiple offline HPLC-FC setups, which are labour-intensive and time-consuming. That is problematic during, e.g., large sports events, where reporting time is limited (e.g., 72Â h). Therefore, in the current work, we developed a uniform online 2D/3D HPLC-FC method, capable of purifying all relevant target compounds in a single run, leading to the fastest clean-up procedure so far (i.e., 31Â min for T and its main metabolites; 46Â min for 19-NA, F and 6aOHADION; 48Â min for B and BM).
Lenka Honesova, Peter Van Eenoo, Michael Polet
1690 related Products with: A uniform sample preparation procedure for gas chromatography combustion isotope ratio mass spectrometry for all human doping control relevant anabolic steroids using online 2/3-dimensional liquid chromatography fraction collection.25 µg1.0 mg100 TESTS10ìg 100ul 100ul5 mg0.1 mg0.1 mg0.1 mg20 ug 100ul
#33817997 2021/04/05 To Up
Longitudinal evaluation of multiple biomarkers for the detection of testosterone gel administration in women with normal menstrual cycle.In women, hormonal fluctuations related to the menstrual cycle may impose a great source of variability for some biomarkers of testosterone (T) administration, which can ultimately disrupt the sensitivity of their longitudinal monitoring. In this study, the sensitivity of the current urinary and haematological markers of the Athlete Biological Passport (ABP), as well as serum steroid biomarkers, was investigated for the monitoring of a 28-day T gel treatment combined with endogenous fluctuation of the menstrual cycle in 14 healthy female subjects. Additionally, the analysis of urinary target compounds was performed on a subset of samples for endogenous/exogenous origin via isotope ratio mass spectrometry (IRMS). In serum, concentrations of T and dihydrotestosterone (DHT) increased significantly during the treatment, whereas in urine matrix the most affected biomarkers were found to be the ratios of testosterone/epitestosterone (T/E) and 5Î±-androstane-3Î±,17Î²-diol/epitestosterone (5Î±Adiol/E). The detection capability of both urinary biomarkers was heavily influenced by [E], which fluctuated depending on the menstrual cycle, and resulted in low sensitivity of the urinary steroidal ABP module. On the contrary, an alternative approach by the longitudinal monitoring of serum T and DHT concentrations with the newly proposed T/androstenedione ratio showed higher sensitivity. The confirmatory IRMS results demonstrated that less than one third of the tested urine samples fulfilled the criteria for positivity. Results from this study demonstrated that the 'blood steroid profile' represents a powerful complementary approach to the 'urinary module' and underlines the importance of gathering bundle of evidence to support the scenario of an endogenous prohibited substance administration.
Olivier Salamin, Raul Nicoli, Tobias Langer, Julien Boccard, Carine Schweizer Grundisch, Cheng Xu, Serge Rudaz, Tiia Kuuranne, Nelly Pitteloud, Martial Saugy
2933 related Products with: Longitudinal evaluation of multiple biomarkers for the detection of testosterone gel administration in women with normal menstrual cycle.
#33527655 2021/02/11 To Up
Cell culture as a toolbox to generate phase I metabolites for antidoping screening.The knowledge of the biotransformation of compounds prohibited by the World Anti Doping Agency is of high concern as doping analyses are mostly based on the detection of metabolites instead of the parent compounds abused by athletes. While the self-administration of doping-relevant compounds is from an ethical point of view a rather problematic method to investigate metabolism, the usage of cell culture systems allows for studies on biotransformation in vitro. Five cell culture models with different tissue origin (liver, ovary, skin, kidney, and testis) were comparatively incubated with testosterone and epitestosterone as well as with the synthetic testosterone derivatives 17Î±-methyltestosterone and 4-chlorotestosterone to investigate the impact of synthetic modifications on phase I metabolic pathways. Cell culture supernatants were analyzed by high-performance liquid chromatography-tandem mass spectrometry. All cell lines possessed the default steroid phase I biotransformation reactions. The highest conversion rate was observed in ovarian (BG-1) and liver cells (HepG2). For BG-1 and skin cells (HaCaT), the 5Î±-reductase products 5Î±-dihydrotestosterone (for both) and 5Î±-androstane-3Î±/Î²,17Î²-diol (for BG-1 solely) were found to be prevailing after testosterone incubation. In kidney (COS-1) and HepG2 cells, the 17Î²-hydroxysteroid dehydrogenase activity was predominant as supported by the observation that the 17Î±-OH (epitestosterone) and the methyl group (17Î±-methyltestosterone) impeded the conversion rate in these cell lines. In conclusion, future work should extend the characterization of the BG-1 and HepG2 cells on phase II metabolic pathways to examine whether they are suitable models for the generation of metabolite reference collections comparable to those obtained by human excretion studies.
Ryan Savill, Helge Baues, Emmely Voigt, Oliver Zierau, Detlef Thieme, Annekathrin Martina Keiler
2522 related Products with: Cell culture as a toolbox to generate phase I metabolites for antidoping screening.1 kit1 kit100 assays96 samples100 assays96 assays100 assays24 tests100 extractions100 assays
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#32578357 2020/09/01 To Up
Evaluation of longitudinal steroid profiling with the ADAMS adaptive model for detection of transdermal, intramuscular, and subcutaneous testosterone administration.The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites in order to identify samples suspicious for the use of synthetic forms of endogenous anabolic androgenic steroids (EAAS). Samples identified by the module may then be confirmed by isotope ratio mass spectrometry (IRMS) to establish clearly the exogenous origin of testosterone and/or metabolites in the sample. To examine the detection capability of the steroidal ABP model, testosterone administration studies were performed with various doses and three routes of administration - transdermal, intramuscular, and subcutaneous with 15 subjects for each route of administration. Urine samples were collected before, during, and after administration and steroid profiles were analyzed using the steroidal ABP module in ADAMS. A subset of samples from each mode of administration was also analyzed by IRMS. The steroidal ABP module was more sensitive to testosterone use than population-based thresholds and with high dose administrations there was very good agreement between the IRMS results and samples flagged by the module. However, with low dose administration the ABP module was unable to identify samples where testosterone use was still detectable by IRMS analysis. The testosterone/epitestosterone (T/E) ratio was the most diagnostic parameter for longitudinal monitoring with the exception of low testosterone excretors for whom the 5Î±-androstane-3Î±, 17Î²-diol/epitestosterone (5Î±Adiol/E) ratio may provide more sensitivity.
Vinod S Nair, Jacob Husk, Geoffrey D Miller, Peter van Eenoo, Andre Crouch, Daniel Eichner
1332 related Products with: Evaluation of longitudinal steroid profiling with the ADAMS adaptive model for detection of transdermal, intramuscular, and subcutaneous testosterone administration.5 G2x96 well plate100 mg1kit2000 rxn1 mg200 units
#32540072 2020/05/23 To Up
Steroid profiling in urine of intact glucuronidated and sulfated steroids using liquid chromatography-mass spectrometry.Detection of endogenous anabolic androgenic steroids (EAAS) misuse is a major challenge in doping control analysis. Currently, a number of endogenous steroids, which constitute the steroid profile, are quantified using gas chromatography (GC). With this methodology, only the sum of the free and glucuronidated steroids is measured together. A dilute-and-shoot LC-MS method, which is compliant with the quality requirements for measuring EAAS established by the World Anti-Doping Agency (WADA), was developed and validated containing glucuronidated and sulfated steroids in order to gain some extra information and to expand the existing steroid profile. The developed method is, to the best of our knowledge, the first method to combine both steroid glucuronides and sulfates, which is compliant with the quality standards of the technical document on EAAS, established by WADA. The first advantage of this new steroid profile is the reduced sample preparation time, as it is a direct injection method of diluted urine. A second advantage is the ability of the used gradient to separate 5Î±-androstane-3Î±,17Î²-diol-3-glucuronide (5Î±Î±Î²diol3G), 5Î±-androstane-3Î±,17Î²-diol-17-glucuronide (5Î±Î±Î²diol17G), 5Î²-androstane-3Î±,17Î²-diol-3-glucuronide (5Î²Î±Î²diol3G) and 5Î²-androstane-3Î±,17Î²-diol-17-glucuronide (5Î²Î±Î²diol17G) allowing to gain specific information on these isomers, which cannot be accomplished in GC-MS screening due to hydrolysis. This steroid profile also contains free testosterone, 5Î±-androstane-3,17-dione and 5Î²-androstane-3,17-dione as markers of degradation. In total, 17 compounds and 10 isotopically labelled internal standards are included in this method.
Laurie De Wilde, Kris Roels, Pieter Van Renterghem, Peter Van Eenoo, Koen Deventer
2359 related Products with: Steroid profiling in urine of intact glucuronidated and sulfated steroids using liquid chromatography-mass spectrometry.20 500 20 20 0.5 mg20 100 1 mg100 20 100 1 ml
#32265631 2020/03/20 To Up
Learning and the Lifespan: What's Sex Got to Do With It?Engagement in sexual behavior can impact neurosteroidogenesis, in particular production of the prohormone testosterone (T) and likely its subsequent metabolism to 5Î±-androstane-3Î±-17Î²-Diol (3Î±-Diol) or aromatization to estradiol (E). Androgens and their metabolites vary across the lifespan and impact many behaviors, including cognition, anxiety, and sexual behavior. Thus, we hypothesized that mating may alter cognitive performance via androstane neurosteroids in an age- and experience-dependent manner. We first investigated if exposure to mating during memory consolidation could enhance performance in the novel object recognition task (NOR). Male rats were trained in NOR and then immediately exposed to mating-relevant or control stimuli. Following a 4 h inter-trial interval (ITI), male rats were tested for object memory. Male rats that were exposed to a receptive female during the ITI had better performance in NOR. We then investigated if these effects were due to novelty associated with mating. Male rats were exposed to mating-relevant stimuli and identified as sexually responsive (SR) or sexually non-responsive (SNR) based on a median split of engagement in mating with the stimulus female. We found that a brief history (10 min session daily for five consecutive days) of sexual history substantially influenced performance in the NOR task, such that SR males had better performance in the NOR task, but only when presented with the opportunity to mate during the ITI. As T levels substantially decrease with age in male rodents, we investigated whether the effects of long-term sexual experience (10 months) influenced neurosteroids and NOR performance in mid-aged (12 months old) males. Mid-aged SR males maintain neural T; however, they have decreased neural E and decreased cognitive performance at 12 months compared to mid-aged SNR rats. In sexually experienced rats, those with better cognitive performance had greater levels of T metabolites (e.g., 3Î±-Diol in mated SR males, E in mid-aged SNR rats). While naÃ¯ve males that were mated during the ITI had better cognitive performance, T metabolites were decreased compared to controls. These findings suggest that T metabolites, but not the prohormone, may influence learning dependent on sexual proclivity, experience, and proximate opportunity to mate.
Amy Stave Kohtz, Cheryl A Frye 1 G100ug1 mg96T30 m Pcs Per Pack1ml
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