Artificial Oxygen Carriers - The New Doping Threat in Endurance Sport?

Schumacher, Yorck Olaf; Schmid, A.; Dinkelmann, S.; Berg, Ansgar; Northoff, Hinnak

doi:10.1055/s-2001-18560

Cited by 25 publications

(15 citation statements)

References 42 publications

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“…(R 1 , R 2 , R 6 = CH 2 CH 2 OH). medical purpose of oxygen therapeutics, abuse of those compounds is possible, especially in sporting activities requiring enormous endurance performance in order to improve oxygen transport during competition [175,176].…”

Section: Hemoglobin-based Oxygen Carriers (Hbocs)mentioning

confidence: 99%

Mass Spectrometry in Doping Control Analysis

Thevis¹,

Schänzer

2005

COC

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Mass spectrometry has become the most frequently employed technique in doping control analysis to identify prohibited compounds ever since their use has been banned by international federations. In combination with gas or liquid chromatography and various ionization methods such as electron or chemical ionization, electrospray, atmospheric pressure chemical ionization, atmospheric pressure photo ionization or matrix-assisted laser desorption ionization, numerous applications have been established enabling the sensitive and selective detection of prohibited drugs in matrices such as urine, blood, and hair. The classes of investigated compounds include low molecular weight drugs such as anabolic steroids, diuretics, β 2 -agonists and β-receptor blocking agents, and others as well as high molecular weight therapeutics, for instance plasma volume expanders based on polysaccharide structures (e.g. hydroxyethyl starch and dextran), hemoglobin-based oxygen therapeutics (e.g. Hemopure), or synthetic insulins. Assays for their identification are commonly based on extractive purification, chemical or enzymatic treatment (i.e. derivatization or degradation) followed by chromatographic and mass spectrometric analysis employing various modern analyzers such as quadrupole, ion trap, triple-quadrupole and magnetic-sector mass spectrometers allowing the sensitive and unambiguous qualitative as well as quantitative determination of xenobiotics in elite athletes' doping control samples. Moreover, the administration of drugs naturally occurring in human beings, for instance testosterone, is uncovered by carbon isotope ratio mass spectrometry that enables the differentiation between endogenous and exogenous sources. The comparison of δ-values obtained from endogenously produced steroids independent from testosterone and its metabolism with urinary testosterone and its metabolic products allow the determination of surreptitious applications.

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Section: Hemoglobin-based Oxygen Carriers (Hbocs)mentioning

confidence: 99%

Mass Spectrometry in Doping Control Analysis

Thevis¹,

Schänzer

2005

COC

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“…However, to date less than 10 products have been under clinical consideration (Table 2), a fact that stresses the challenging requirements artificial blood substitutes have to fulfill (Vandegriff et al, 2003;Greenburg and Kim, 2004;Standl, 2005). Although scientific data about the effect of HBOCs on endurance and athletic performance is very limited and skepticism regarding a positive influence is prevalent (Schumacher et al, 2001;Schumacher and Ashenden, 2004), artificial oxygen carriers are considered relevant for doping controls. Numerous studies have been published demonstrating the determination of HBOCs in human plasma by means of various techniques such as 1D-gel electrophoresis , size-exclusion chromatography combined with UV detection (Gotzmann et al, 2002;VarletMarie et al, 2004) as well as different mass spectrometric approaches (Thevis et al, 2003;Gasthuys et al, 2004Gasthuys et al, , 2005Goebel et al, 2005 a,b).…”

Section: Hemoglobin-based Oxygen Carriers (Hbocs)mentioning

confidence: 99%

Identification and Characterization of Peptides and Proteins in Doping Control Analysis

Thevis¹,

Schänzer

2005

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Analysis of peptides and proteins has become an important component of doping control laboratories. Several peptide hormones such as insulin, insulin-like growth factor-I, growth hormone, erythropoietin, and hemoglobin-based oxygen carriers are considered to possess an enormous potential to artificially increase athletic performance and belong to the list of prohibited compounds and methods established by regulatory authorities such as the World Anti-Doping Agency (WADA). In order to reveal abuse of those drugs in professional as well as amateur sports, doping control laboratories have been developing various strategies to identify target analytes in blood or urine specimens employing different biochemical techniques such as immunoaffinity purification, isoelectric focusing, gel electrophoresis, double-blotting as well as concomitant top-down and bottom-up mass spectrometry based proteomic approaches. These enable the qualitative determination of derivatives of naturally occurring peptides and proteins such as insulin and hemoglobin as well as possibilities to distinguish between endogenously produced and presumably identical recombinant proteins such as growth hormone and erythropoietin. Most applied strategies are common proteomics procedures, but they have been modified to meet the specific requirements and limitations of doping control, i.e. type of specimens, available amounts, required specificity and sensitivity, unambiguousness of results, and speed of analysis.

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“…Blood substitutes, while showing some benefit, are readily detected ( Schumacher et al ., 2001 ). Synthetic Hb and HBOCs impart a red colour to serum, thereby simplifying detection.…”

Section: Agents Used In Dopingmentioning

confidence: 99%

Erythropoiesis‐stimulating agents and other methods to enhance oxygen transport

Elliott

2008

British J Pharmacology

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Oxygen is essential for life, and the body has developed an exquisite method to collect oxygen in the lungs and transport it to the tissues. Hb contained within red blood cells (RBCs), is the key oxygen-carrying component in blood, and levels of RBCs are tightly controlled according to demand for oxygen. The availability of oxygen plays a critical role in athletic performance, and agents that enhance oxygen delivery to tissues increase aerobic power. Early methods to increase oxygen delivery included training at altitude, and later, transfusion of packed RBCs. A breakthrough in understanding how RBC formation is controlled included the discovery of erythropoietin (Epo) and cloning of the EPO gene. Cloning of the EPO gene was followed by commercial development of recombinant human Epo (rHuEpo). Legitimate use of this and other agents that affect oxygen delivery is important in the treatment of anaemia (low Hb levels) in patients with chronic kidney disease or in cancer patients with chemotherapy-induced anaemia. However, competitive sports was affected by illicit use of rHuEpo to enhance performance. Testing methods for these agents resulted in a cat-and-mouse game, with testing labs attempting to detect the use of a drug or blood product to improve athletic performance (doping) and certain athletes developing methods to use the agents without being detected. This article examines the current methods to enhance aerobic performance and the methods to detect illicit use.

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Artificial Oxygen Carriers - The New Doping Threat in Endurance Sport?

Cited by 25 publications

References 42 publications

Mass Spectrometry in Doping Control Analysis

Mass Spectrometry in Doping Control Analysis

Identification and Characterization of Peptides and Proteins in Doping Control Analysis

Erythropoiesis‐stimulating agents and other methods to enhance oxygen transport

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