Detection of the selective androgen receptor modulator andarine (S‐4) in a routine equine blood doping control sample

Cawley, Adam; Smart, Corrine; Greer, Candace; Lau, M.; Keledjian, John

doi:10.1002/dta.1867

Cited by 18 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 occurrences of SARMs were reported which correspond to almost 10% and 18%, respectively, of the total AAFs in the S1.2 drug class. 30,31 Due to their considerable variety of chemical core structure and the exhibition of substantially different physicochemical properties, the generation of data for SARMs related to the substances' ionization and dissociation under commonly utilized analytical conditions in doping control laboratories, is crucial to routine sports drug testing. 30,31 Due to their considerable variety of chemical core structure and the exhibition of substantially different physicochemical properties, the generation of data for SARMs related to the substances' ionization and dissociation under commonly utilized analytical conditions in doping control laboratories, is crucial to routine sports drug testing.…”

mentioning

confidence: 99%

Human in vivo metabolism study of LGD‐4033

Fragkaki

Sakellariou

Kiousi

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

Selective androgen receptor modulators (SARMs) are an emerging class of therapeutics targeted to cachexia, sarcopenia, and hypogonadism treatment. LGD-4033 is a SARM which has been included on the Prohibited List annually released by the World Anti-Doping Agency (WADA). The aim of the present work was the investigation of the metabolism of LGD-4033 in a human excretion study after administration of an LGD-4033 supplement, the determination of the metabolites' excretion profiles with special interest in the determination of its long-term metabolites, and the comparison of the excretion time of the phase I and phase II metabolites. The results were also compared to those derived from previous LGD-4033 studies concerning both in vitro and in vivo experiments. Supplement containing LGD-4033 was administered to one human male volunteer and urine samples were collected up to almost 21 days. Analysis of the hydrolyzed (with β-glucuronidase) as well as of the non-hydrolyzed samples was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in negative ionization mode and revealed that, in both cases, the two isomers of the dihydroxylated metabolite (M5) were preferred target metabolites. The glucoconjugated parent LGD-4033 and its gluco-conjugated metabolites M1 and M2 can be also considered as useful target analytes in non-hydrolyzed samples. The study also presents two trihydroxylated metabolites (M6) identified for the first time in human urine; one of them was recently reported in an LGD-4033 metabolism study in horse urine and plasma. KEYWORDS human doping, LGD-4033, liquid chromatography-mass spectrometry, SARM, selective androgen receptor modulator

show abstract

mentioning

confidence: 99%

Human in vivo metabolism study of LGD‐4033

Fragkaki

Sakellariou

Kiousi

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…The rapid increase in the prevalence of designer anabolic steroids present in ‘dietary’ and ‘nutritional’ supplements available online containing untested and unapproved anabolic agents, or the more recent emergence of selective androgen receptor modulators (SARMs), is likely to pose a significant threat to the integrity of the industry if left unchecked. Both drug classes present several problems for anti‐doping laboratories resulting from their widely variable structures that will need to be addressed in the future.…”

Section: Future Directionsmentioning

confidence: 99%

A review of designer anabolic steroids in equine sports

Waller

McLeod

2016

Drug Testing and Analysis

View full text Add to dashboard Cite

In recent years, the potential for anabolic steroid abuse in equine sports has increased due to the growing availability of designer steroids. These compounds are readily accessible online in 'dietary' or 'nutritional' supplements and contain steroidal compounds which have never been tested or approved as veterinary agents. They typically have unusual structures or substitution and as a result may pass undetected through current anti-doping screening protocols, making them a significant concern for the integrity of the industry. Despite considerable focus in human sports, until recently there has been limited investigation into these compounds in equine systems. To effectively respond to the threat of designer steroids, a detailed understanding of their metabolism is needed to identify markers and metabolites arising from their misuse. A summary of the literature detailing the metabolism of these compounds in equine systems is presented with an aim to identify metabolites suitable for incorporation into screening protocols by anti-doping laboratories. The future of equine anti-doping research is likely to be guided by the incorporation of alternate testing matrices into routine screening, the improvement of in vitro technologies that can mimic in vivo equine metabolism, and the improvement of instrumentation or analytical methods that allow for the development of untargeted screening, and metabolomics approaches for use in anti-doping screening protocols.

show abstract

“…Blood samples were collected at time 0 (immediately prior to SARM administration) and at 5, 10, 15, 30, and 45 min, and 1, 1.5, 2, 2.5, 3,4,5,6,8,12,18,24,48,72 and 96 h post SARMs administration. Prior to drawing each sample of blood for analysis, 10 mL of blood was aspirated and discarded from the catheter and T-Port extension set Figure 1.…”

Section: Administration and Sample Collectionmentioning

confidence: 99%

“…[5] There has also been one report of a positive case of illicit SARM use in equine sports. [6] This is a clear indication that there is a need for a better understanding of the excretion profiles and metabolite patterns of SARMs in horses. For substances that undergo extensive biotransformation, metabolic studies are necessary in order to find analytical targets for doping control and thereby to prolong the detection times.…”

mentioning

confidence: 99%