Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children

1 Apr 1998

Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2 : a phase I study in children / Catherine Pihoker, Gregory L. Kearns, Daniel French, Cyril Y. Bowers

  • Journal of Clinical Endocrinology & Metabolism, 83 (1998) 4 (1 April), p. 1168-1172
  • PMID: 9543135
  • DOI: 10.1210/jcem.83.4.4744


Administration of GH-releasing peptide-2 (GHRP-2) represents a potential mode of therapy for children of short stature with inadequate secretion of GH. Requisite information to determine the dosing route and frequency for GHRP-2 consists of the pharmacokinetics (PK) and pharmacodynamics (PD) for this compound, neither of which have been previously evaluated in children. The purpose of this study was to characterize the PK and PD of GHRP-2 in children with short stature. Ten prepubertal children (nine boys and one girl; 7.7 +/- 2.4 yr old) received a single 1 microg/kg i.v. dose of GHRP-2 over 1 min, followed by repeated (n = 9) blood sampling over 2 h. GHRP-2 and GH were quantitated by specific RIA methods. PK parameters were calculated from curve fitting of GHRP-2 and GH vs. time data. Posttreatment plasma GH concentrations (normalized for pretreatment values) were used as the effect measurement. PD parameters were generated using the sigmoid Emax model. Disposition of GHRP-2 best fit a biexponential function. GHRP-2 PK parameters (mean +/- SD) were: alpha = 13.4 +/- 9.7 h(-1), beta = 1.3 +/- 0.3 h(-1), t(1/2beta) = 0.55 +/- 0.14 h, AUC(0-infinity) = 2.02 +/- 1.37 ng/mL x h, Cmax = 7.4 +/- 3.8 ng/mL, plasma clearance = 0.66 +/- 0.32 L/h x kg, and apparent volume of distribution = 0.32 +/- 0.14 L/kg. PK parameters for GH were: appearance rate constant = 5.9 +/- 3.1 h(-1), elimination t(1/2) = 0.37 +/- 0.15 h, lag time = 0.05 +/- 0.01 h, Cmax = 50.7 +/- 17.2 ng/mL, Tmax = 0.42 +/- 0.16 h, and AUC(0-infinity) = 47.9 +/- 26.1 ng/mL x h. PD parameters for GHRP-2 were: Ke0 = 1.13 +/- 0.94 h(-1), gamma = 13.15 +/- 9.44, E0 = 6.63 +/- 4.86 ng/mL (GH), Emax = 67.5 +/- 23.5 ng/mL (GH), and EC50 = 1.09 +/- 0.59 ng/mL. We concluded that 1) GHRP-2 produced a predictable and significant (i.e. compared to pretreatment values) increase in plasma GH concentrations; 2) the PK-PD link model enabled quantitative assessment of GHRP-2 modulation of serum GH levels; and 3) definition of the EC50 for GHRP-2 will enable PD and PK evaluations of extravascular dosing regimens for children.

Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry

16 Jun 2010

Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry / Masato Okano, Mitsuhiko Sato, Ayako Ikekita, Shinji Kageyama

  • Rapid Communications in Mass Spectrometry 24 (2010) 14 (30 July), p. 2046-2056
  • PMID: 20552695
  • DOI: 10.1002/rcm.4619


GHRP-2 (pralmorelin, D-Ala-D-(beta-naphthyl)-Ala-Ala-Trp-D-Phe-Lys-NH(2)), which belongs to a class of growth hormone secretagogue (GHS), is intravenously used to diagnose growth hormone (GH) deficiency. Because it may be misused in expectation of a growth-promoting effect by athletes, the illicit use of GHS by athletes has been prohibited by the World Anti-Doping Agency (WADA). Therefore, the mass spectrometric identification of urinary GHRP-2 and its metabolite D-Ala-D-(beta-naphthyl)-Ala-Ala-OH (AA-3) was studied using liquid chromatography/electrospray ionization tandem mass spectrometry for doping control purposes. The method consists of solid-phase extraction using stable-isotope-labeled GHRP-2 as an internal standard and subsequent ultra-performance liquid chromatography/tandem mass spectrometry, and the two target peptides were determined at urinary concentrations of 0.5-10 ng/mL. The recoveries ranged from 84 to 101%, and the assay precisions were calculated as 1.6-3.8% (intra-day) and 1.9-4.3% (inter-day). Intravenous administration of GHRP-2 in ten male volunteers was studied to demonstrate the applicability of the method. In all ten cases, unchanged GHRP-2 and its specific metabolite AA-3 were detected in urine.

A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men

1 Oct 1998

A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men / E.A. Nijland, C.J. Strasburger, C. Popp-Snijders, P.S. van der Wal, E.A. van der Veen

  • European Journal of Endocrinology 139 1998 4 (October), p. 395-401
  • PMID: 9820615
  • DOI: 10.1530/eje.0.1390395


The synthetic hexapeptide growth hormone-releasing peptide (GHRP)-2 specifically stimulates GH release in man. To determine the effects of prolonged treatment and whether response attenuation occurs in man, we administered to nine healthy subjects a daily s.c. injection of 100 microg GHRP-2 over 5 days. Every day blood samples were taken to determine GH, IGF-I, IGF-binding protein (IGFBP)-3 and osteocalcin levels. On days 1,3 and 5, GH was measured at -20,0,20,40,60,90,120 and 180 min using an immunometric and an immunofunctional assay. Mean-/+S.D). peak GH concentrations were 83+/-31, 59+/-22 and 51+/-13 microg/l on days 1, 3 and 5 respectively. Mean+/-S.D. areas under the curve for days 1, 3 and 5 were 6366+/-2514, 3987 +/- 1418 and 3392+/-1215 mU/l per min. Despite the maintained GH release, analysis of variance revealed that significant response attenuation occurred (P < 0.01). Mean serum IGF-I concentration did not increase after a 5 day treatment with GHRP-2. Mean basal levels were 22, 25,23,25,23,24 nmol/l measured on days 1 to 6. However, osteocalcin, another serum marker of GH activity in tissue, increased significantly from 3.2+/-1.0 to 4.2+/-0.4 microg/l (mean+S.D.) (P< 0.01).

Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays

24 Apr 2018

Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays / Annekathrin Martina Keiler, Oliver Zierau, Sylvi Wolf, Patrick Diel, Wilhelm Schänzer, Günter Vollmer, David Machalz, Gerhard Wolber, Maria Kristina Parr

  • Toxicology Letters 292 (August 2018), p. 39-45
  • PMID: 29702199
  • DOI: 10.1016/j.toxlet.2018.04.026


4-Hydroxyandrost-4-ene-3,17-dione, also named formestane, is an irreversible aromatase inhibitor and therapeutically used as anti-breast cancer medication in post-menopausal women. Currently, no therapeutical indication led to approval of its 17-hydroxylated analog 4-hydroxytestosterone, an anabolic steroid. However, it is currently investigated in a clinical trial for breast cancer. In context with sports doping, aromatase inhibitors are administered to reduce estrogenic side effects of misused anabolic substances or their metabolites. Therefore, both substances are prohibited in sports by the World Anti-Doping Agency (WADA). Analysis of urinary phase I and phase II metabolites showed similar results for both compounds. In the current investigation, 4-hydroxyandrost-4-ene-3,17-dione, 4-hydroxytestosterone and seven of their described urinary metabolites as well as 2α-hydroxyandrostenedione were tested in the yeast androgen screen and the yeast estrogen screen. Androgenic effects were observed for all tested substances, except for one, which showed anti-androgenic properties. With regard to the yeast estrogen screen, estrogenic effects were observed for only two metabolites at rather high concentrations, while six out of the ten substances tested showed anti-estrogenic properties. In terms of the strong androgenic effect observed for 4-hydroxytestosterone (10-8 M), 4-hydroxyandrost-4-ene-3,17-dione (10-8 M) and two more urinary metabolites, the yeast androgen assay may also be used to trace abuse in urine samples.

The potential of urinary androstdiene markers to identify 4-androstenediol (4-ADIOL) administration in athletes

21 Dec 2010

The potential of urinary androstdiene markers to identify 4-androstenediol (4-ADIOL) administration in athletes / Adam T. Cawley , Graham J. Trout, Rymantas Kazlauskas, Adrian V. George

  • Forensic Science International 208 (2011) 1-3 (20 May), p. 129-138
  • PMID: 21177052
  • DOI: 10.1016/j.forsciint.2010.11.016


Doping control laboratories accredited by the World Anti-Doping Agency (WADA) require criteria that allow endogenous steroids to be distinguished from their synthetic analogues in urine. Methodology based on "looking outside the metabolic box" was used in this study to identify diagnostic urinary markers of 4-androstenediol (4-ADIOL) administration. Androst-2,4-diene-17-one and androst-3,5-diene-17-one are proposed to be formed in urine from acid-catalyzed hydrolysis of 4-ADIOL sulfoconjugate, a major phase II metabolic product of 4-ADIOL. The presence of these markers in the routine gas chromatography-mass spectrometry (GC-MS) steroid screen was suitable to identify samples requiring confirmation by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) - to measure the carbon isotope ratio (δ(13)C) of the androstdiene markers and confirm their likely synthetic origin based on depleted (13)C content.

17beta-hydroxy-5alpha-androst-1-en-3-one (1-testosterone) is a potent androgen with anabolic properties

18 Apr 2016

17beta-hydroxy-5alpha-androst-1-en-3-one (1-testosterone) is a potent androgen with anabolic properties / A. Friedel, H. Geyer, M. Kamber, U. Laudenbach-Leschowsky, W. Schänzer, M. Thevis, G. Vollmer, O. Zierau, P. Diel

  • Toxicology Letters 165 (2006) 2 (August), p. 149-155
  • PMID: 16621347
  • DOI: 10.1016/j.toxlet.2006.03.001


Since the begining of the year 2005, the use of steroid precursors (prohormones) is illegal in the United States; nevertheless, there is still an enormous abuse of such substances. One of the most frequently misused steroids, often declared to be a prohormone, is 1-testosterone (17beta-hydroxy-5alpha-androst-1-en-3-one, 1-Testo). In this study, we have characterised molecular mechanisms of its action, determined its tissue specific androgenic and anabolic potency and investigated potential adverse effects. 1-Testo binds highly selective to the androgen receptor (AR) and has a high potency to stimulate AR dependent transactivation. In vivo an equimolar dose of 1-Testo has the same potency to stimulate the growth of the prostate, the seminal vesicles and the androgen sensitive levator ani muscle as the reference compound testosterone propionate (TP). Administration of 1-Testo, in contrast to TP, results in a significant increase of liver weight. Our results demonstrate that 1-Testo, even without being metabolised, is a very potent androgen. It binds selectively to the AR and transactivates AR dependent reporter genes. In vivo it has a high androgenic and anabolic potency and increases liver weight. In summary 1-Testo can be characterised as a typical anabolic steroid. It has to be assumed that consumption of this substance is associated with adverse side effects typical for this class of compounds. Therefore, a strict control of its ban is essential.

Detection of dehydroepiandrosterone misuse by means of gas chromatography- combustion-isotope ratio mass spectrometry

1 Dec 2007

Detection of dehydroepiandrosterone misuse by means of gas chromatography- combustion-isotope ratio mass spectrometry / Ute Mareck, Hans Geyer, Ulrich Flenker, Thomas Piper, Mario Thevis, Wilhelm Schänzer

  • European Journal of Mass Spectrometry 13 (2007) 6 (December), p. 377-384
  • PMID: 18417762
  • DOI: 10.1255/ejms.900


According to World Anti-Doping Agency (WADA) rules (WADA Technical Document-TD2004EAAS) urine samples containing dehydroepiandrosterone (DHEA) concentrations greater than 100 ng ML(-1) shall be submitted to isotope ratio mass spectrometry (IRMS) analysis. The threshold concentration is based on the equivalent to the glucuronide, and the DHEA concentrations have to be adjusted for a specific gravity value of 1.020. In 2006, 11,012 doping control urine samples from national and international federations were analyzed in the Cologne doping control laboratory, 100 (0.9%) of them yielding concentrations of DHEA greater than 100 ng mL(-1). Sixty-eight percent of the specimens showed specific gravity values higher than 1.020, 52% originated from soccer players, 95% were taken in competition, 85% were male urines, 99% of the IRMS results did not indicate an application of testosterone or related prohormones. Only one urine sample was reported as an adverse analytical finding having 319 ng mL(-1) DHEA (screening result), more than 10,000 ng mL(-1) androsterone and depleted carbon isotope ratio values for the testosterone metabolites androsterone and etiocholanolone. Statistical evaluation showed significantly different DHEA concentrations between specimens taken in- and out-of- competition, whereas females showed smaller DHEA values than males for both types of control. Also a strong influence of the DHEA excretion on different sport disciplines was detectable. The highest DHEA values were detected for game sports (soccer, basketball, handball, ice hockey), followed by boxing and wrestling. In 2007, 6622 doping control urine samples were analyzed for 3alpha,5-cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo), a DHEA metabolite which was described as a useful gas chromatography-mass spectrometry (GC-MS) screening marker for DHEA abuse. Nineteen urine specimens showed concentrations higher than the suggested threshold of 140 ng mL(-1), six urine samples yielded additionally DHEA concentrations higher than 100 ng mL(-1), none of them showing positive IRMS findings. These results should be taken into consideration in future discussions about threshold values for endogenous steroids in doping control.

Identification of the anabolic steroid 6β-chlorotestosterone in a dietary supplement

20 Sep 2018

Identification of the anabolic steroid 6β-chlorotestosterone in a dietary supplement / Travis M. Falconer, Rick A. Flurer, Mary B. Jones, Lisa M. Lorenz, Sarah E. Voelker

  • Drug Testing and Analysis 11 (2019) 3 (March), p. 422-427
  • PMID: 30238638
  • DOI: 10.1002/dta.2510


Capsules that were labeled to be performance-enhancing dietary supplements obtained during an investigation were found to contain an unrecognized steroid-like substance. This compound was isolated by liquid chromatography (LC) fraction collection and characterized using several qualitative analytical techniques, including ultraviolet (UV) spectroscopy, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-high resolution accurate mass-mass spectrometry (LC-HRAM-MS), as well as 1 H, 13 C, and two-dimensional nuclear magnetic resonance (NMR) spectrometry. This multi-technique analytical approach was used to identify the designer steroid as 6β-chloro-4-androsten-17β-ol-3-one (6β-chlorotestosterone), an analog of testosterone about which little has been published.

CAS 2021_A_8056 Olga Pestova vs RUSADA

23 May 2022

CAS 2021/A/8056 Olga Pestova v. Russian Anti-Doping Agency (RUSADA)

  • Rugby
  • Doping (methylhexaneamine)
  • Conditions for the reduction of the standard sanction on the basis of “No Significant Fault or Negligence”
  • Level of care expected from the athlete for a finding of “No Significant Fault or Negligence”
  • Categories and levels of fault

1. According to the applicable regulations, in order for the standard sanction for a violation involving a specified substance and a non-intentional anti-doping rule violation to be reduced on the basis of “No Significant Fault or Negligence”, the athlete must, on a balance of probabilities, firstly establish how the prohibited substance entered his/her system (the so-called “route of ingestion”). This is the “threshold” condition established by the anti-doping rules to allow “access” to a finding of “No Significant Fault or Negligence”. Secondly, s/he must establish the facts and circumstances that are relevant to his/her fault and, on that basis, why the standard sanction should be reduced. A period of ineligibility can be reduced based on “No Significant Fault or Negligence” only in cases where the circumstances justifying a deviation from the duty of exercising the “utmost caution” are truly exceptional, and not in the vast majority of cases.

2. The “bar” should not be set too high for a finding of “No Significant Fault or Negligence”. In other words, a claim of “No Significant Fault or Negligence” is (by definition) consistent with the existence of some degree of fault and cannot be excluded simply because the athlete left some “stones unturned”. An athlete can always read the label of the product used or make internet searches to ascertain its ingredients, cross-check the ingredients so identified against the Prohibited List or consult with the relevant sporting or anti-doping organizations, consult appropriate experts in anti-doping matters and, eventually, not take the product. However, an athlete cannot reasonably be expected to follow all such steps in every and all circumstances. To find otherwise would render the “No Significant Fault or Negligence” provision in the World Anti-Doping Code (WADC) and translated into the applicable regulations meaningless.

3. Until the 2015 version of the WADC, anti-doping rules allowed a distinction between three degrees of fault or negligence. The 2015 version of the WADC significantly differs from the previous scheme for the consideration of the specificities of individual cases. As a result, the time span of 24 months which is still available now covers only two instead of three categories of fault: 1) normal degree of fault: over 12 months and up to 24 months with a standard normal degree leading to an 18-month period of ineligibility; and 2) light degree of fault: 0-12 months with a standard light degree leading to a 6-month period of ineligibility. In order to determine into which category of fault a particular case might fall, it is helpful to consider both “objective” and “subjective” levels of fault. The objective level of fault points to “what standard of care could have been expected from a reasonable person in the athlete’s situation”, while the subjective level looks to “what could have been expected from that particular athlete, in the light of his/her particular capacities”. Therefore, the objective element should be foremost in determining into which of the relevant categories a particular case falls; the subjective element can then be used to move a particular athlete up or down within that category. All in all, however, there might be some overlap within those elements.

In October 2020 the Russian Anti-Doping Agency (RUSADA) reported an anti-doping rule violatin against the rugby player Olga Pestova after her sample tested positive for the prohibited substance Methylhexaneamine (1,3-dimethylamylamine).

Consequently on 19 May 2021 the RUSADA Disciplinary Anti-Doping Committee (DADC) decided to impose a 1 year period of ineligibility on the Athlete. The DADC accepted that the violation was not intentional and considered that at the material time the Athlete suffered from a head injury that effected her physical and psychological condition.

Hereafter in June 2021 the Athlete appealed the DADC decision with the Court of Arbitration for Sport (CAS). She requested the Panel to set aside the Appealed Decision and to eliminate or reduce the imposed sanction.

The Athlete admitted the violation and denied the intentional use of the substance. She explained that she suffered from a head injury a week before the match and the sample collection.

After her injury she did not receive a proper examination and she continued to train while she experienced acute headache, nausea and dizziness. Feeling sick and disoriented she consumed a Melior sport drink purchased in a sport nutrition shop.

She asserted that she did check the ingredients of this drink and only after further research into this product it appeared that this Melior drink was a counterfeit product of Russian origin. She acknowledged that she did not inform the team's managagement about her medical condition because she feared not to be selected for the next match.

The Athlete argued that her cognitive disorder caused by concussion is of particular relevance to assess whether she could adequately evaluate the information and make decisions when she bought and consumed the Melior sport drink.

RUSADA accepted that the Athlete's violation was not intentional and that the Melior sport drink was the possible source of the prohibited substance in her sample. Yet it does not accept that the Athlete has demonstrated that her judgement or decision-making capacity was, in any event, impaired by her head injury.

The Sole Arbitrator finds that it is undisputed between the Parties that the Athlete has committed an anti-doping rule violation and has demonstrated how the substance had entered her system.

Following assessment of the Athlete's conduct impaired by her head injury the Sole Arbitrator deems that there is no justification for a further reduction of the imposed sanction.

Therefore the Court of Arbitration for Sport decides on 23 May 2022 that:

1. The appeal filed by Ms Olga Pestova with the Court of Arbitration for Sport against the decision issued on 13 May 2021 by the Disciplinary Anti-Doping Committee of the Russian Anti-Doping Agency is dismissed.

2. The decision issued on 13 May 2021 by the Disciplinary Anti-Doping Committee of the Russian Anti-Doping Agency is confirmed.

3. (…).

4. (…).

5. All other prayers for relief are dismissed.

CAS 2021_A_7840 WADA vs ICF & Aleksandra Dupik

9 Jun 2022

CAS 2021/A/7840 World Anti-Doping Agency (WADA) v. International Canoe Federation (ICF) & Aleksandra Dupik

  • Canoeing
  • Doping (furosemide)
  • Use of a prohibited substance
  • Standard of proof
  • Methods of proof
  • Circumstantial evidence
  • Reduction of the period of disqualification in the interests of fairness

1. It is made clear by Article 2.2.1 of the ICF 2009 Anti-Doping Regulations (ADR) that, because it is every athlete’s duty to ensure that no prohibited substance enters his or her body, it is not necessary to show that any use on the part of an athlete was intentional or knowing, or that an athlete was at fault in some way or that he or she failed to take due care (i.e., was negligent).

2. The standard of proof of comfortable satisfaction is greater than a mere balance of probability, but less than proof beyond a reasonable doubt. The more serious the allegation, the more cogent the supporting evidence must be in order for the allegation to be found proven. However, contrary to what is often asserted, the standard itself does not change; it is the required cogency of the evidence that changes on the basis that the more serious the allegations (a) the less likely that the alleged fact or event has occurred and (b) the more serious the consequences. The standard of proof remains to the comfortable satisfaction of the Panel bearing in mind the seriousness of the allegations.

3. As a general rule, facts relating to anti-doping rule violations (ADRV) may (i.e., it is permissible) be established by “any reliable means”. This rule gives greater leeway to anti-doping organisations to prove violations, so long as they can comfortably satisfy a tribunal that the means of proof is reliable. As a result, it is not even necessary that a violation be proven by a scientific test itself. Instead, a violation may be proved through admissions, testimony of witnesses, or other documentation evidencing a violation. This rule is not a requirement that the evidence adduced be “reliable evidence”. Rather, it is a rule as to the method or manner or form in which the facts that are necessary to sustain an allegation of an ADRV may be established, and the rule provides (in a non-exhaustive list) a number of examples of means of establishing facts which are characterised as “reliable”.

4. In case there is no direct but only circumstantial evidence, the adjudicatory body must assess the evidence separately and together and must have regard to what is sometimes called “the cumulative weight” of the evidence. It is in the nature of circumstantial evidence that single items of evidence may each be capable of an innocent explanation but, taken together, establish guilt beyond reasonable doubt. There may be a combination of circumstances, no one of which would raise a reasonable conviction, or more than a mere suspicion, but the whole taken together, may create a strong conclusion of guilt.

5. Article 10.8 of the ICF 2009 ADR provides that all competitive results achieved by the athlete from the date that a positive sample was collected or other ADRV was committed through to the start of the period of ineligibility is to be disqualified with all of the resulting consequences as there set forth – unless fairness requires otherwise. Indeed in certain exceptional circumstances, the strict application of the disqualification rule can produce an unjust result. In particular, this may be the case when the potential disqualification period covers a very long term, which is normally the case when the facts leading to the ADRV took place long before the adjudicating proceedings started which usually occurs when they are opened as a result of the re-testing of a sample or of the uncover of a sophisticated doping scheme. In addition, in this type of cases it may be difficult to prove that the athlete at stake used prohibited substances or methods during such a long period of time.

In 2016, Professor Richard McLaren issued two reports about systemic doping in Russia. These reports identified a significant number of Russian athletes who were involved in, or benefitted from, the doping schemes and practices that he uncovered.

Hereafter in January 2019 the World Anti-Doping Agency (WADA) recovered the internal database of the Moscow Laboratory (LIMS). Following investigation of allegations of organized doping practices, and in particular of the LIMS, WADA provided international federations with investigation reports on the athletes implicated in these organized doping practices.

These investigation reports revealed that the prohibited substances Furosemide had been established in the sample of the Athlete Aleksandra Dupik. This sample was provided by the Athlete in April 2014 and thereupon deliberately reported as negative by the Moscow laboratory.

However the ICF concluded that there was insufficient direct evidence that the Athlete had committed an anti-doping rule violation and decided on 11 March 2021 not to bring forward this case.

Hereafter in March 2021 the World Anti-Doping Agency (WADA) appealed the ICF decision with the Court of Arbitration for Sport (CAS). WADA requested the Panel to set aside the Appealed Decision and to impose a period of ineligibility on the Athlete from 2 to 4 years.

WADA contended that the evidence in relation to the Athlete's samples clearly showed that the Athlete committed an anti-doping rule violation and that the decision by the ICF not to move forward with this matter was manifestly wrong.

The Athlete denied that she had committed an anti-doping rule violation and argued that the appeal should be dismissed and the Appealed Decision should be confirmed. Further she disputed the reliability of the filed evidence in this case provided by WADA, Professor McLaren and Dr Rodchenkov.

There was no pleaded challenge to the manner in which the ICF conducted itself in coming to its decision, only that its decision was wrong. The appeal was therefore conducted by the Parties as an inquiry into whether the evidence was sufficient to establish, to the applicable standard of proof, that the Athlete had committed an anti-doping rule violation and not as to whether the ICF had met its investigation obligations under its anti-doping rules and related international standards.

Following assessment of all evidence provided by the Parties, the Panel concludes as follows:

  • There was a systemic cover-up and manipulation of the doping control process within Russia in the manner described by Prof. McLaren in the McLaren Reports, commonly referred to as the Russian doping scheme.
  • The Moscow Laboratory performed both initial testing procedures and confirmation procedures on the Sample, the results of which showed the presence of the diuretic, Furosemide.
  • Furosemide is a prohibited substance.
  • In furtherance of the Russian doping scheme, and in order to protect the Athlete from the consequences of the positive test result, the Moscow Laboratory recorded the analytical results of the Sample in ADAMS as negative.
  • In relation therefore to the ADRV allegations in this matter, the Panel concludes that, upon taking the evidence as a whole and assessing its cumulative weight, the Panel is comfortably satisfied that, on or about 19 April 2014, the Athlete used a prohibited substance (namely, Furosemide) in violation of Article 2.2(b) of the 2009 ICF ADR.

Therefore the The Court of Arbitration for Sport decides on 9 June 2022 that:

1.) The appeal filed by the World Anti-Doping Agency on 1 April 2021 against the International Canoe Federation and Ms Aleksandra Dupik with respect to the decision rendered by the International Canoe Federation on 11 March 2021 is upheld.

2.) The decision rendered on 11 March 2021 by the International Canoe Federation in the matter of Ms Aleksandra Dupik is set aside.

3.) Ms Aleksandra Dupik is found to have committed an anti-doping rule violation under Article 2.2 of the International Canoe Federation’s 2009 Anti-Doping Rules.

4.) Ms Aleksandra Dupik is sanctioned with a period of ineligibility of two (2) years starting from the date of this Award.

5.) All competitive results achieved by Ms Aleksandra Dupik from 19 April 2014 through to and including 31 December 2016 are disqualified with all of the resulting consequences, including the forfeiture of any titles, awards, medals, points and prize and appearance money.

6.) (…).

7.) (…).

8.) All other or further requests for relief are hereby dismissed.

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