Liquid chromatography – high resolution mass spectrometry-based metabolomic approach for the detection of Continuous Erythropoiesis Receptor Activator effects in horse doping control

Joré, Céline; Loup, Benoît; Garcia, Patrice; Paris, A.; Popot, Marie-Agnès; Audran, Michel; Bonnaire, Yves; Varlet‐Marie, Emmanuelle; Bailly-Chouriberry, Ludovic

doi:10.1016/j.chroma.2017.09.029

Cited by 17 publications

(23 citation statements)

References 55 publications

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“…Another alternative was the analysis of the effects on metabolome resulting from the administration of the continuous erythropoiesis receptor activator. In order to do that, metabolic fingerprints were recorded by LC‐HRMS in plasma 327 and urine 326,327 …”

Section: Resultsmentioning

confidence: 99%

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Doping detection in animals: A review of analytical methodologies published from 1990 to 2019

Moreira

Carmo

Pinho

et al. 2021

Drug Testing and Analysis

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Despite the impressive innate physical abilities of horses, camels, greyhounds, or pigeons, doping agents might be administered to these animals to improve their performance. To control these illegal practices, anti‐doping analytical methodologies have been developed. This review compiles the analytical methods that have been published for the detection of prohibited substances administered to animals involved in sports over 30 years. Relevant papers meeting the search criteria that discussed analytical methods aiming to detect and/or quantify doping substances in animal biological matrices published from 1990 to 2019 were considered. A total of 317 studies were included, of which 298 were related to horses, demonstrating significant advances toward the development of doping detection methods for equine sports. However, analytical methods for the detection of doping agents in sports involving other species are lacking. Due to enhanced accuracy and specificity, chromatographic analysis coupled to mass spectrometry detection is preferred over immunoassays. Regarding biological matrices, blood and urine remain the first choice, although alternative biological matrices, such as hair and feces, have been considered. With the increasing number and type of drugs used as doping agents, the analytes addressed in the published papers are diverse. It is very important to continue to detect and quantify these drugs, recognizing those that are most frequently used, in order to punish the abusers, protect animals' health, and ensure a healthier and genuine competition.

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Section: Resultsmentioning

confidence: 99%

“…LC‐HRMS based on orbitrap technology has been successfully used for the screening of large sets of doping agents, both in equine urine 373 and in plasma 23 . The description of the use of LC‐HRMS based on time‐of‐flight (TOF) technology was presented in a few papers published in peer‐reviewed journals 326,327,374 …”

Section: Resultsmentioning

confidence: 99%

Doping detection in animals: A review of analytical methodologies published from 1990 to 2019

Moreira

Carmo

Pinho

et al. 2021

Drug Testing and Analysis

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“…Similarly, 1-cyclopentenoylglycine may be a new biomarker of testosterone misuse [16]. In horses, several biomarkers have been identified to detect the misuse of the erythropoiesis receptor activator [10].…”

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confidence: 99%

Identification of metabolomic changes in horse plasma after racing by liquid chromatography-high resolution mass spectrometry as a strategy for doping testing

Ueda

Tozaki

Nozawa

et al. 2019

JES

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Recently, the illegal use of novel technologies, such as gene and cell therapies, has become a great concern for the horseracing industry. As a potential way to control this, metabolomics approaches that comprehensively analyze metabolites in biological samples have been gaining attention. However, it may be difficult to identify metabolic biomarkers for doping because physiological conditions generally differ between resting and exercise states in horses. To understand the metabolic differences in horse plasma between the resting state at training centres and the sample collection stage after racing for doping test (SAD), we took plasma samples from these two stages (n=30 for each stage) and compared the metabolites present in these samples by liquid chromatography-high resolution mass spectrometry. This analysis identified 5,010 peaks, of which 1,256 peaks (approximately 25%) were annotated using KEGG analysis. Principal component analysis showed that the resting state and SAD groups had entirely different metabolite compositions. In particular, the levels of inosine, xanthosine, uric acid, and allantoin, which are induced by extensive exercise, were significantly increased in the SAD group. In addition, many metabolites not affected by extensive exercise were also identified. These results will contribute to the discovery of biomarkers for detecting doping substances that cannot be detected by conventional methods.

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“…In addition, there are currently lack of effective means for the detection of prohibited practices, such as inhalation of xenon or krypton gas, and extracorporeal shockwave therapy 14 . Monitoring the changes in biomarkers that are associated with the effects of prohibited substances or practices provides an indirect approach for their detection 15–17 . The biomarker‐based approach has the potential to control different classes of substances or practices that produce a similar effect.…”

Section: Introductionmentioning

confidence: 99%

“…14 Monitoring the changes in biomarkers that are associated with the effects of prohibited substances or practices provides an indirect approach for their detection. [15][16][17] The biomarker-based approach has the potential to control different classes of substances or practices that produce a similar effect. In recent years, WADA has adopted several biomarker tests to control the misuse of anabolic steroids, human growth hormone, and erythropoiesis-stimulating agents (ESAs) in human athletes.…”

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confidence: 99%

Label‐free proteomics for discovering biomarker candidates of RAD140 administration to castrated horses

Cheung

Wong

et al. 2021

Drug Testing and Analysis

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Selective androgen receptor (AR) modulators (SARMs) are potent anabolic agents with a high potential of misuse in horseracing and equestrian sports. In this study, we applied label-free proteomics to discover plasma protein biomarkers in geldings (castrated horses) after administration with a popular SARM named RAD140. Tryptic peptides were prepared from plasma samples and analyzed by nano-flow ultrahighperformance liquid chromatography-high-resolution tandem mass spectrometry (nano-UHPLC-HRMS/MS) using data-independent acquisition (DIA) method. Orthogonal projection on latent structure-discriminant analysis (OPLS-DA) has led to the development of a predictive model that could discriminate RAD140-administered samples from control samples and could also correctly classify 18 out of 19 intraining horses as control samples. The model comprises 75 proteins with variable importance in projection (VIP) score above 1. Gene Ontology (GO) enrichment analysis and literature review have identified upregulation of AR-regulated clusterin, and proteins associated with inflammation (haptoglobin, cluster of differentiation 14 [CD14], and inter-alpha-trypsin inhibitor heavy chain 4 [ITIH4]) and erythropoiesis (glycosylphosphatidylinositol-specific phospholipase D1 [GPLD1]) after RAD140 administration. Their changes were confirmed by selected reaction monitoring (SRM) experiments. Similar effects have been reported by the use of androgens and otherSARMs. This is the first reported study that describes the use of a proteomic biomarker approach to detect horses that have been administered with RAD140 by applying label-free proteomic profiling of plasma samples. These results support the concept of a biomarker-driven approach to enhance the doping control of RAD140 and potentially other SARMs in the future.

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Liquid chromatography – high resolution mass spectrometry-based metabolomic approach for the detection of Continuous Erythropoiesis Receptor Activator effects in horse doping control

Cited by 17 publications

References 55 publications

Doping detection in animals: A review of analytical methodologies published from 1990 to 2019

Doping detection in animals: A review of analytical methodologies published from 1990 to 2019

Identification of metabolomic changes in horse plasma after racing by liquid chromatography-high resolution mass spectrometry as a strategy for doping testing

Label‐free proteomics for discovering biomarker candidates of RAD140 administration to castrated horses

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