Use Of Selective Androgen Receptor Modulators Research Articles

Advances in SARMs anti-doping analysis.

Selective androgen receptor modulators (SARMs) are performance-enhancing drugs (PEDs) that stimulate anabolism, increase muscle mass and strength and promote recovery from exercise. The use of SARMs in sports is considered doping and is strictly prohibited by the World Anti-Doping Agency (WADA) and the International Federation of Horseracing Authorities (IFHA). To monitor the abuse of SARMs in sports, it is essential to develop advanced, selective and sensitive analytical methods that provide reliable results. This review evaluates the advances in this area, with a focus on the identification of target analytes related to SARMs, such as SARMs, their metabolites or markers. The aim is to identify targets that could extend the detection windows of SARMs, provide scientific support for results management and/or offer an indirect biomarker-based approach to doping control. This review also aims to evaluate the current liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods developed for the monitoring of SARMs in different biological matrices, including traditional matrices such as urine and serum/plasma samples, as well as alternative matrices such as dried blood spots, hair and nail samples.

Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers.

Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding. To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers. Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance. The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products. Most websites reported misleading information; specifically, the statement "for research only" was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of "broscience" as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim. The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed. This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated. SARMs sold online as food supplement-like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.

In vitro metabolism study of a black market product containing SARM LGD-4033.

Anabolic agents are often used by athletes to enhance their performance. However, use of steroids leads to considerable side effects. Non-steroidal selective androgen receptor modulators (SARMs) are a novel class of substances that have not been approved so far but seem to have a more favourable anabolic/androgenic ratio than steroids and produce fewer side effects. Therefore the use of SARMs has been prohibited since 2008 by the World Anti-Doping Agency (WADA). Several of these SARMs have been detected on the black market. Metabolism studies are essential to identify the best urinary markers to ensure effective control of emerging substances by doping control laboratories. As black market products often contain non-pharmaceutical-grade substances, alternatives for human excretion studies are needed to elucidate the metabolism. A black market product labelled to contain the SARM LGD-4033 was purchased over the Internet. Purity verification of the black market product led to the detection of LGD-4033, without other contaminants. Human liver microsomes and S9 liver fractions were used to perform phase I and phase II (glucuronidation) metabolism studies. The samples of the in vitro metabolism studies were analyzed by gas chromatography-(tandem) mass spectrometry (GC-MS(/MS)), liquid chromatography-high resolution-tandem mass spectrometry (LC-(HR)MS/MS). LC-HRMS product ion scans allowed to identify typical fragment ions for the parent compound and to further determine metabolite structures. In total five metabolites were detected, all modified in the pyrrolidine ring of LGD-4033. The metabolic modifications ranged from hydroxylation combined with keto-formation (M1) or cleavage of the pyrrolidine ring (M2), hydroxylation and methylation (M3/M4) and dihydroxylation (M5). The parent compound and M2 were also detected as glucuronide-conjugates. Copyright © 2016 John Wiley & Sons, Ltd.

Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC–MS/MS

Selective androgen receptor modulators (SARMs) represent a novel class of drugs with tissue-specific agonistic and antagonistic properties, which are prohibited in sports from January 2008 according to the World Anti-Doping Agency. Preventive approaches to restrict the use of SARMs include early implementation of target analytes into doping control screening assays. Five model SARMs were synthesized, four of which are analogs to prostate-specific androgen receptor antagonists with a 5,6-dichloro-benzimidazole nucleus. The fifth SARM is a muscle-tissue specific agonist with a bicyclic hydantoin structure (BMS-564929). Dissociation pathways after negative electrospray ionization were studied using an LTQ-Orbitrap mass analyzer, and diagnostic product ions and common fragmentation patterns were employed to establish a screening procedure that target the intact SARMs as well as putative metabolic products. Sample preparation based on solid-phase extraction and subsequent LC-MS/MS measurement allowed for detection limits of 1-20 ng/mL, intra- and interday precisions of between 2.4 and 13.2% and between 6.5 and 24.2%, respectively. Recoveries varied from 89 to 106%, and tests for ion suppression or enhancement effects were negative for all analytes. [figure: see text]

What is past is prologue: estrogen/progestin replacement tomorrow

Hormone Replacement17beta-ESTRADIOLSelective Estrogen Receptor ModulatorsEstrogen SulfamatesPhytoestrogensHybrid ProgestinsSelective Progesterone ReceptorModulatorsNon-MASCULINIZING Androgen