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"meldonium Problems" of a Russian Professional Tennis Player Maria Sharapova

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Maria Sharapova is a Russian professional tennis player who has won five grand slam championships. On January 26th, 2016 she completed a drug test and in June 2016 her career took a negative turn she received a letter informing her that she tested positive for the drug meldonium, which goes by the brand name mildronate (Meher, Das, & Mahanty, 2017). Meldonium was classified as a performance-enhancing drug under the metabolic modulator class by the World Anti-Doping Agency on January 1st, 2016 and was previously in the monitoring program (Meldonium, 2016). This drug became a major issue for many athletes as by April 13th, 2016 170 athletes had tested positive for having meldonium in their systems (Meldonium, 2016).

This topic relates to drug testing because routine drug testing performed by the World-Anti-Doping Agency caught all of these athletes using meldonium and assigned them what they believed to be their appropriate consequences. Maria Sharapova was originally given a two-year suspension from the sport of tennis from the international tennis federation. Meldonium is an over the counter medication in Eastern Europe but is not approved in North America or Western Europe. In Eastern Europe this drug was originally invented as a growth-promoting agent for animals but within the last 40 years it was found to have anti-ischemic, cardioprotective effects and the ability to increase sperm motility and sexual performance (Meher, Das, & Mahanty, 2017)( Gorgens, Guddat, Dib, Geyer, Schanzer & Thevis, 2015).

The reason that this drug has been banned by the World Anti-Doping Agency is because it is believed to have performance-enhancing effects due to its ability to change the way carnitine is metabolized in the body and its ability to increase the relative metabolic rate of glucose oxidation. This drug is effective because it binds to the enzyme gamma-butyrobetaine hydroxylase and inhibits it from biosynthesizing carnitine, which decreases the plasma carnitine levels. This affects the body because carnitine carries fatty acids into the mitochondria for energy and with lower plasma carnitine levels this does not occur. and this leads to a vasodilatory response. The other effect that meldonium has is that it increases the relative metabolic rate of glucose oxidation and this is where most of the performance enhancing benefits are believed to come from. An increase in the relative metabolic rate of glucose oxidation needs less oxygen to complete the process than fatty acid oxidation and this can lead to the improvement of cardiac myocytes also known as muscle cells under ischemic conditions (Meldonium, 2016).

Although this drug does have many benefits for cardiac health and performance enhancement it also has some risks involved with it. Due to the decrease in plasma carnitine levels there is a possibility for a deficiency. A carnitine deficiency can cause muscle ache, fatigue, muscular weakness, cramps at exertion and can induce hypoketotic hypoglycaemia, which can be unfavourable for nervous and muscular function (Jargin, 2016). In addition to these risks some studies in the Soviet Union have shown that carnitine exerts a cardioprotective effect in cardiomyopathy, it helps lessen the infarct size, it prevents arrhythmias, improves survival in myocardial infarction patients, and increases exercise tolerance in angina and heart failure patients (Buszewski,& Noga).

The reason that this is important is because when your body has a carnitine deficiency these positive effects that carnitine has, may not occur putting your body at risk if you suffer from certain illnesses or diseases. To test athletes for the use of meldonium urine samples are used. After the urine is collected a hydrophilic interaction liquid chromatography-tandem mass spectrometry test is used for initial detection. After this, a hydrophilic interaction liquid chromatography high resolution/high accuracy mass spectrometry test is used to confirm suspicious initial testing results (Gorgens, Guddat, Dib, Geyer, Schanzer & Thevis, 2015).

To break the testing technique into more understandable terms I have defined hydrophilic interaction liquid chromatography, Tandem mass spectrometry and high resolution/high accuracy mass spectrometry below. Hydrophilic interaction liquid chromatography is a powerful separation technique that separates polar compounds on polar stationary phases. This technique has become very popular in bioanalytical applications because drugs and their metabolites such as meldonium are often polar structures (Buszewski, B., & Noga, S) (Meldonium).

Tandem mass spectrometry is a technique used to breakdown-selected ions into fragments to reveal aspects of the chemical structure (Tandem Mass Spectrometry, 2015). Lastly, high resolution/high accuracy mass spectrometry is defined as an instrument that is capable of distinguishing ions that differ by just a fraction of a mass unit (High Resolution, 2007). Overall, these are very accurate techniques for the World Anti-Doping Agency to use to ensure fair and accurate results for all athletes tested.There is one main complication with meldonium that has caused some debate. This is that limited data existed on the urinary excretion of meldonium when it was added to the prohibited list. When meldonium was first introduced as a prohibited drug several studies were being conducted involving the world Anti-Doping Agency accredited laboratories but the results had yet to have been released.

The information that they did have from the preliminary results of the studies showed urinary concentrations higher than 10 μg/mL stayed in the system up to 72 hours and this was the first elimination phase. This was followed by a long-term excretion or second elimination phase, yielding concentrations up to approximately 2 μg/mL over the following three weeks. Last, long-term urinary excretion below 1 μg/mL down to several hundred ng/mL could persist for a number of weeks and in the low tens of ng/mL for a few months. Due to the lack of clear scientific evidence a hearing panel might find that an athlete who ingested meldonium before January 1st, 2016 may not have known or suspected that the meldonium would still be present in his or her body on or after January 1st, 2016.

To combat this issue guidelines were set in place. The guidelines stated, If the concentration is between 1 and 15 μg/mL and the test was taken before March 1st, 2016, or if the concentration is below 1 μg/mL and the test was taken after March 1st, 2016 the world anti-doping agency may find there to be grounds for no fault or negligence on the part of the athlete because the results of ongoing excretion studies are needed to determine the time of the ingestion. With this being said if the sample tested positive during competition they would still be disqualified (Notice-Meldonium, April 2016). On June 30th, 2016 an updated notice was released after further urinary excretion studies had been completed although other studies were ongoing and unpublished.

This notice was specifically for cases where athletes claim that the substance was taken before January 1st, 2016. It stated that if you had urinary concentrations of meldonium below 1 μg/mL, for samples collected on or before September 30th, 2016, results management may proceed and a finding of no fault may be made, if it was between 5 and 15 μg/mL, for samples collected on or before February 29th, 2016, and concentrations between 1 and 5 μg/mL for samples collected between March 1st and September 20th, 2016 you can contact the Science Department at for assistance facilitating scientific review and interpretation. If levels were above 0.1 μg/mL (or 100 ng/mL), for samples collected after September 30th, 2016, normal results management shall proceed in accordance with the World Anti-Doping Code and the relevant ADO’s rules (Notice-Meldonium, June 2016).

Although Maria Sharapova was given a two-year ban from tennis she did report an appeal to the court of arbitration for sport but she did not appeal for the controversy explained above. She claimed her offence to be unintentional because she had been using the drug for 10 years to help with her irregular heartbeat, family history of diabetes and frequent cases of the flu and did not realize that it has been added to the restricted substances list (Hattenstone, 2017). This did come with some scrutiny because the manufacturer of the drug did not include influenza or diabetes on their list of uses for meldonium (Cohen, 2016). With all of this information after the appeal, her ban was reduced to 15 months (Hattenstone, 2017).

References:

  1. Buszewski, B., & Noga, S. Hydrophilic Interaction Liquid Chromatography (HILC)-A Powerful Seperation Technique. Springer. 402(1), 231-247. doi: 10.1007/s00216-011-5308-5
  2. Cohen, E. (2016, June 8). The Secret Cold War Origins of Sharapova’s Doping. CNN. Retrieved from https://www.cnn.com/2016/03/21/health/maria-sharapova-drug-meldonium-cold-war-origins/index.html
  3. Gorgens, C., Guddat, S., Dib, J., Geyer, H., Schanzer, W., & Thevis, M. (2015) Mildronate (Meldonium) in professional sports – monitoring doping control urine samples using hydrophilic interaction liquid chromatography – high resolution/high accuracy mass spectrometry. Drug Testing and Analysis Wiley Online Library. 7, 973-979. doi: 10.1002/dta.1788
  4. Jargin, S. V. (2016). Meldonium (mildronate): primum non nocere. Pharmacological Research. 114(1), 294. doi: https://doi.org/10.1016/j.phrs.2016.10.004
  5. Meher, B. R., Das, S., & Mahanty, R. R. (2017). Meldonium: drug which brought disrepute to sport. International Journal of Basic & Clinical Pharmacology, 6(8), 1841-1845. doi:http://dx.doi.org/10.18203/2319-2003.ijbcp20173267
  6. Meldonium (mildronate): A Performance Enhancing Drug?. American College of Clinical Pharmacology, 5(3), 167-169. doi:10.1002/cpdd.264Meldonium. PubChem. Retrieved from: https://pubchem.ncbi.nlm.nih.gov/compound/Mildronate#section=TopHattenstone, s. (2017, September 9).
  7. Maria Sharapova on failing that drug test: ‘I felt trapped, tricked.’ The Guardian. Retrieved from https://www.theguardian.com/sport/2017/sep/09/maria-sharapova-failing-drug-test-felt-trapped-tricked
  8. Shang, R., Sun, Z., & Li, H. (2014). Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovascular Disorders. 14(1), 1-7. doi:10.1186/1471-2261-14-88(2007).
  9. High Resolution Mass Spectrometry. Bio compare. Retrieved from: https://www.biocompare.com/Editorial-Articles/41598-High-Resolution-Mass-Spectrometry/(2015).
  10. Tandem Mass Spectrometry. National High Magnetic Field Laboratory. Retrieved from: https://nationalmaglab.org/user-facilities/icr/techniques/tandem-ms(April 2016).
  11. Notice-Meldonium. World Anti-Doping Agency. Retrieved from: https://www.wada-ama.org/sites/default/files/resources/files/wada-2016-04-12-meldonium-notice-en.pdf(June 2016).
  12. Notice-Meldonium. World Anti-Doping Agency. Retrieved from: https://www.wada-ama.org/sites/default/files/resources/files/2016-06-30-meldonium_notice.pdf (2016).

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“Meldonium Problems” Of A Russian Professional Tennis Player Maria Sharapova. (2020, May 19). GradesFixer. Retrieved October 26, 2020, from https://gradesfixer.com/free-essay-examples/meldonium-problems-of-a-russian-professional-tennis-player-maria-sharapova/
““Meldonium Problems” Of A Russian Professional Tennis Player Maria Sharapova.” GradesFixer, 19 May 2020, gradesfixer.com/free-essay-examples/meldonium-problems-of-a-russian-professional-tennis-player-maria-sharapova/
“Meldonium Problems” Of A Russian Professional Tennis Player Maria Sharapova. [online]. Available at: <https://gradesfixer.com/free-essay-examples/meldonium-problems-of-a-russian-professional-tennis-player-maria-sharapova/> [Accessed 26 Oct. 2020].
“Meldonium Problems” Of A Russian Professional Tennis Player Maria Sharapova [Internet]. GradesFixer. 2020 May 19 [cited 2020 Oct 26]. Available from: https://gradesfixer.com/free-essay-examples/meldonium-problems-of-a-russian-professional-tennis-player-maria-sharapova/
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