Mildronate (Meldonium) in professional sports : monitoring doping control urine samples using hydrophilic interaction liquid chromatography - high resolution/high accuracy mass spectrometry / Christian Görgens, Sven Guddat, Josef Dib, Hans Geyer, Wilhelm Schänzer, Mario Thevis. - (Drug Testing and Analysis 7 (2015) 11-12 (November-December) p. 973-979)

• DOI: 10.1002/dta.1788

Content:

- Introduction
- Experimental
• Chemicals and reagents
• Synthesis of labelled IS
• Sample preparation
• LC-MS/MS
* Initial testing
* Confirmatory analysis
• Method validation
• Routine doping control samples
- Results and discussion
• Mass spectrometry
• Liquid chromatography
• Method validation
• Routine doping control samples
- Conclusion

Abstract:

To date, substances such as Mildronate (Meldonium) are not on the radar of anti-doping laboratories as the compound is not explicitly classified as prohibited. However, the anti-ischemic drug Mildronate demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of central nervous system (CNS) functions.
In the present study, the existing evidence of Mildronate’s usage in sport,which is arguably not exclusively) based onmedicinal reasons, is corroborated by unequivocal analytical data allowing the estimation of the prevalence and extent of misuse in professional sports. Such data are vital to support decision-making processes, particularly regarding the ban on drugs in sport. Due to the growing body of evidence (black market products and athlete statements) concerning its misuse in sport, adequate test methods for the reliable identification of Mildronate are required, especially since the substance has been added to the 2015 World Anti-Doping Agency (WADA) monitoring program.
In the present study, two approaches were established using an in-house synthesized labelled internal standard (Mildronate-D3). One aimed at the implementation of the analyte into routine doping control screening methods to enable its monitoring at the lowest possible additional workload for the laboratory, and another that is appropriate for the peculiar specifics of the analyte, allowing the unequivocal confirmation of findings using hydrophilic interaction liquid chromatography-high resolution/high accuracy mass spectrometry (HILIC-HRMS). Here, according to applicable regulations in sports drug testing, a full qualitative validation was conducted. The assay demonstrated good specificity, robustness (rRT=0.3%), precision (intra-day: 7.0–8.4%; inter-day: 9.9–12.9%), excellent linearity (R>0.99) and an adequate lower limit of detection (<10 ng/mL).

Mind sports and doping : an investigation of pharmacological substances that may enhance performance in mind sports [2000] / Olivier de Hon, F. Hartgens. – Capelle aan den IJssel : Netherlands Centre for Doping Affairs (NeCeDo), 2000

As a result of the ratification of the Anti-Doping Convention in 1995, the Dutch government has increasingly compelled the national sports federations to pursue an active anti-doping policy. As a minimum, these federations must have anti-doping regulations. However, mind sports (chess, draughts, bridge, and Go) have provisionally been exempted from this ruling because there are doubts about the relevance of this policy to these sports. In response to a request from the Dutch federations of various mind sports, the Dutch Ministry of Health, Welfare, and Sport has asked the Netherlands Centre for Doping Affairs to investigate whether pharmacological substances can be used to enhance performance in mind sports.

Conclusions:
• The factors that determine performance are substantially different between mind sports and physical sports, and this justifies separate anti-doping regulations.
• In the world of mind sports itself, the impression exists that pharmacological substances are used only sporadically to enhance performance.
• It can be expected that performance in mind sports can be enhanced by means of pharmacological substances; however, the expected effect of such substances is minor.
• Some of the possible performance-enhancing substances may be harmful to health, which means that these substances should be considered as doping agents.
• It is recommended that the mind sports federations formally prohibit doping and that these federations draw up regulations that enable sanctions to be imposed when prohibited substances are used in mind sports.
• If the decision is taken to prohibit doping in mind sports, it is recommended that a specific list of prohibited substances be drawn up. The current (IOC) list of prohibited substances should not be used unadapted.
• It is important that national and international anti-doping regulations concerning the mind sports are consistent. This investigation may contribute to the harmonisation of these regulations.

Minderjarigen en het antidopingbeleid – deel 2 / H. Ram

• Tijdschrift voor Sport & Recht (2022) 1, p. 1-10
  
  

In dit tweede deel van dit artikel wordt de jurisprudentie inzake door minderjarige sporters begane dopingovertredingen besproken. Daarbij wordt eerst onderzocht hoe de regels in de Wereld Anti-Doping Code (WADC) die specifiek betrekking heeft op minderjarige sporters, inclusief de specifieke regels die het verloop van dopingcontroles bij minderjarige sporters beheersen, worden toegepast. Vervolgens wordt onderzocht hoe minderjarigheid wordt meegewogen en welke factoren daarbij een rol spelen, in het bijzonder bij het bepalen van de strafmaat. Het artikel sluit af met enige conclusies en een jurisprudentieoverzicht.

Minderjarigen en het antidopingbeleid – deel 1 / H. Ram

• Tijdschrift voor Sport & Recht (2021) 4, p. 79-87
  
  

Na een korte introductie wordt in dit artikel een overzicht gegeven van regelgeving in de Wereld Anti-Doping Code (WADC) die specifiek betrekking heeft op minderjarige sporters, en van specifieke regels die het verloop van dopingcontroles bij minderjarige sporters beheersen. Het merendeel van deze regels is van kracht geweest sinds de eerste versie van de WADC, maar een aantal regels is sindsdien gewijzigd of toegevoegd. Vervolgens wordt een aantal gegevens gepresenteerd die inzicht geven in de daadwerkelijke uitvoering van dopingcontroles bij minderjarigen. Het artikel wordt afgesloten met een bespreking van jurisprudentie inzake begeleidend personeel (zoals trainers, coaches en artsen) die vervolgd en veroordeeld zijn wegens het verstrekken of toedienen van doping aan minderjarige sporters. Tuchtcolleges leggen de maximale straf (levenslange uitsluiting) op als de ernst van de overtreding daar voldoende aanleiding toe geeft. In het tweede deel van dit artikel zal de jurisprudentie inzake door minderjarige sporters zelf begane dopingovertredingen besproken worden.

Misuse of Anabolic Products in Sport: a Retrospective Study of Phone Calls at the Écoute Dopage Anti-doping Hot-line / Nicolas Palmié, Hélène Peyrière, Céline Eiden, Claire Condemine-Piron. - (Thérapie 68 (2013) 1 (Janvier-Février); p. 27–29)

• PMID: 23484657
• DOI: 10.2515/therapie/2013006

Objective.
The aim of this retrospective study was to analyze the calls concerning anabolic products (AP), received at Écoute Dopage, a French anti-doping hot-line.

Methods.
We reviewed all phone calls handled between 2000 and 2008, among them 214 concerned AP. Information collected include demographic data, reason for the phone call, name of AP, characteristic of consumption, adverse reactions.

Results.
Fifteen different AP (mainly testosterone) were reported. Calls concerned information about side-effects (42% of calls), risk for doping (28%), and risk for health (10%), psychological assistance (10%), and legislation (2%). Most calls came from fitness practitioners or bodybuilders (85%). The reason for use was documented in 137 subjects: to increase muscular strength (76%), improve social life ability (15%), improve sporting ability (6%), and losing weight (3%). Eighty subjects (37%) reported at least one side-effect mainly uro-genital (40 cases) or psychic disorders (25 cases), both 15 cases. Among these 80 patients, 17 patients (21.25%) presented signs of AP dependence.

Conclusion.
The abuse of AP in sport is a public health problem well known, but data on the dependence on AAS are sparser. Information
and education should be emphasise to fight against doping.

On 25 January 2013 the Major League Baseball (MLB) received copies of letters from the Miami News Times to various MLB Clubs advising that an article was being prepared asserting that a Player or Players on those teams were involved in the use op Performing Enhancing Substances (PES). On 29 January 2013 the newspaper published the story identifying Anthony Bosch and his Biogenesis practice as having supplied PES to several Major League Players. MLB Player Alex Rodriguez (A-Rod) was mentioned prominently as one of the PES users. The publication of this article captured national attention and set the stage for a public battle between MLB and Rodruquez over the veracity and consequences of those allegations.

On June 3, 2013, MLB and Antony Bosch entered into a mutual cooperation agreement. Bosch promised to proffer truthful information to MLB and testify if necessary regarding any Major League Player or individuals acting on their behalf regarding the acquisition, possession, or use by them of any PES. In exchange, MLB promised to dismiss Bosch and his brother from MLB's civil suit, to not seek testimony or discovery from Bosch family members, and to inform law enforcement agencies of his cooperation.

MLB convened an investigatory interview with Rodriguez on 12 July 2013. At that session, Rodriguez declined to answer any questions about his involvement, if any, with Bosch or Biogenesis on Fifth Amendment grounds. There were no positive tests conducted under the JDA for Rodriguez during the period of October 2010 and August 2013.

Based on the evidence and statements the MLB reported on 5 August 2013 several anti-doping rule violations against the Player Alex Rodriques for the attempted cover-up, possession and use of the prohibited substances: testosterone, human growth hormone (hGH) and IGF-1 (Insulin-like Growth Factor-1). Therefore the MLB suspended the Player for 211 regular-season games, starting on 8 August 2013.
The MLB suspended a total of 13 Mayor League Players in 2013 for violations of the JDA in connection with the Biogenesis baseball scandal. The Player Alex Rodriques appealed the MLB suspension of 5 August 2011 with the MLB Arbitration Panel. He filed documents, arguments and statements in his defence and was heard for the Panel.

Before the Panel, MLB contends that Rodriguez was disciplined for just cause. MLB maintains Rodriguez committed multiple violations of the JDA over the course of three seasons by the continuous use and possession of a variety of PES. MLB asserts the multiple efforts by Rodriguez to obstruct MLB's investigation of his violations of the JDA violated the Basic Agreement. MLB argues adverse inferences be drawn from Rodriguez's failure to testify under oath in this proceeding or present other witnesses to refute the evidence of his misconduct. MLB contends the penalty in this case is appropriate and justified in light of the scope and gravity of the misconduct by Rodriguez, and that the settlements reached with other Players involved in Biogenesis cannot be considered by agreement of the bargaining parties as previously ruled upon by this Panel. Accordingly, MLB urges the grievance be denied.

The Player Alex Rodriguez contends MLB has failed to meet its burden of proving the alleged misconduct by clear and convincing evidence. Rodriguez argues MLB did not show he possessed and used PES and that the testimony by Bosch, his evidence, and digital evidence are inherently unreliable, must be stricken, and can be afforded no weight. Rodriguez contends that science establish he did not use PES. Rodriguez also asserts MLB failed to establish he obstructed MLB's investigation of Biogenesis and Bosch. Rodriguez further maintains that all of the evidence presented by MLB is irrevocably tainted by investigatory misconduct and coercion of witnesses, including Bosch. Finally, Rodriguez claims the suspension is wholly inappropriate when compared to those given other Players with alleged ties to Biogenesis and Bosch. Thus, Rodriguez asks the suspension not be upheld.

The MLB Arbitration Panel concluded, based on the entire record from the arbitration, that MLB has demonstrated with clear and convincing evidence there is just cause to suspend Rodriguez for the 2014 season and 2014 postseason for having violated the JDA by the use and/or possession of testosterone, IGF-1, and hGH over the course of three years, and for the two attempts to obstruct MLB's investigation, which violated Article XII(B) of the Basic Agreement. While this length of suspension may be unprecedented for a MLB Player, so is the misconduct he committed. The suspension imposed by MLB as modified herein is hereby sustained.
Due to Rodriguez was allowed to play during the appeal process, this effectively reduced the suspension from 211 to 162 games - the entirety of the 2014 regular-season schedule. He also shall lose 162 days of pay for the 2014 season.

On 11 January the Major League Baseball Arbitration Panel decided that the Player's grievance is sustained in part and denied in part. The Panel ruled that MLB has just cause to suspend Alexander Rodriguez for the 2014 season and 2014 postseason.

Hereafter the Player challenged the decision in federal court. However on 7 February 2014 Rodriguez announced that he was dropping his lawsuit and accepting his suspension for the 2014 season.

Mol, Annemarie. Moderation or satisfaction? Food ethics and food facts
In: Vandamme, Sofie; van de Vathorst, Suzanne & de Beaufort, Inez: Whose Weight is it Anyway? Essays on Ethics and Eating, Acco Academic Publishers, page 121-312.

The morality incorporated in food advice, especially in food advice meant to prevent obesity, is that eaters should be moderate. What might one say about this, in ethical mode? Is being moderate to be defended on ethical terms, or is calling for moderation moralistic and intrusive and should eaters be liberated from health advisors? In my contribution to the discussion about this nagging question, I will not offer an answer, but argue that it may not be the right question. In doing so, I will draw out the facts incorporated similarly in calls for moderation and in the anti-moralist revolts against them. Why build on these particular facts and not others? There are ever so many facts to do with food and they tend to come with different values attached. The different repertoires that make up nutrition science, have different ways of framing reality and seeking interference. And while moderation (or thrift) is central to one repertoire of fact-values to do with food, satisfaction (following on from pleasure) is central to another. This difference is linked up with different understandings of what a human body is. In calls for ‘moderation’, the human body is cast a greedy beast. To tame this beast, Man’s rational faculties, that is his will and his cognition, have to take control. In the repertoire where ‘satisfaction’ is appreciated as a good, bodies do not need to be controlled but deserve to be trained. As embodied beings, or such is the idea, we gradually develop our sensitivities in interaction with our surroundings. The art, then, is not to suppress our bodies, but to develop a good taste.

Molecular Effects of Supraphysiological Doses of Doping Agents on Health / Esther Imperlini, Annamaria Mancini, Andreina Alfieri, Domenico Martone, Marianna Caterino, Stefania Orrù, Pasqualina Buono. - (Molecular BioSystems 11 (2015) 6 (June); p. 1494-1506).

• PMID: 25787095.
• DOI: 10.1039/c5mb00030k

Abstract

Performance-enhancing drugs (PEDs) gained wide popularity not only among sportsmen but also among specific subsets of population, such as adolescents. Apart from their claimed effects on athletic performance, they are very appealing due to the body shaping effect exerted on fat mass and fat-free mass. Besides the "underestimated" massive misuse of PEDs, the short- as well as long-term consequences of such habits remain largely unrecognized. They have been strictly associated with serious adverse effects, but molecular mechanisms are yet to be elucidated. Here, we analyze the current understanding of the molecular effects of supraphysiological doses of doping agents in healthy biological systems, at genomic and proteomic levels, in order to define the molecular sensors of organ/tissue impairment, determined by their misuse. The focus is put on the anabolic androgenic steroids (AASs), specifically testosterone (T) and its most potent derivative dihydrotestosterone (DHT), and on the peptide hormones, specifically the growth hormone (GH) and the insulin-like growth factor-1 (IGF-1). A map of molecular targets is defined and the risk incidence for human health is taken into account.

Molecularly Imprinted Nanoparticles Assay (MINA) in Pseudo ELISA: An Alternative to Detect and Quantify Octopamine in Water and Human Urine Samples / Ewa Moczko, Richard Díaz, Bernabé Rivas, Camilo García, Eduardo Pereira, Sergey Piletsky, César Cáceres. - (Polymers (Basel) 11 (2019) 9 (13 September); p. 1-13).
- PMID: 31540212.
- DOI: 10.3390/polym11091497

Abstract

In 2004, octopamine was added to the list of drugs banned by the world anti-doping agency (WADA) and prohibited in any sport competition. This work aims to develop a new analytical method to detect octopamine in water and human urine samples. We proposed a pseudo-enzyme-linked immunosorbent assay (pseudo-ELISA) by replacing traditional monoclonal antibodies with molecularly imprinted polymer nanoparticles (nanoMIPs). NanoMIPs were synthesised by a solid-phase approach using a persulfate initiated polymerisation in water. Their performance was analysed in pseudo competitive ELISA based on the competition between free octopamine and octopamine-HRP conjugated. The final assay was able to detect octopamine in water within the range 1 nmol·L-1-0.1 mol·L-1 with a detection limit of 0.047 ± 0.00231 µg·mL-1 and in human urine samples within the range 1 nmol·L-1-0.0001 mol·L-1 with a detection limit of 0.059 ± 0.00281 µg·mL-1. In all experiments, nanoMIPs presented high affinity to the target molecules and almost no cross-reactivity with analogues of octopamine such as pseudophedrine or l-Tyrosine. Only slight interference was observed from the human urine matrix. The high affinity and specificity of nanoMIPs and no need to maintain a cold chain logistics makes the nanoMIPs a competitive alternative to antibodies. Furthermore, this work is the first attempt to use nanoMIPs in pseudo-ELISA assays to detect octopamine.

Moral disengagement and associated processes in performance-enhancing drug use : a national qualitative investigation / Ian D Boardley, Jonathan Grix, Andrew James Dewar. - (Journal of Sports Sciences 32 (2014) 9 (7 April); p. 836-844)

• PMID: 24405120
• DOI: 10.1080/02640414.2013.862842

Abstract

This study investigated psychosocial processes associated with avoidance of health- and morality-based deterrents to performance-enhancing drug (PED) use. In-depth semi-structured interviews were conducted with 64 English male bodybuilders with experience of doping. Resultant data were content analysed deductively using definitions for the eight mechanisms of moral disengagement (MD; Bandura, A. (1991). Social cognitive theory of moral thought and action. In W. M. Kurtines & J. L. Gewirtz (Eds.), Handbook of moral behavior and development: Theory research and applications (pp. 71-129). Hillsdale, NJ: Lawrence Erlbaum Associates.), and three further themes from Boardley and Grix (2013. Doping in bodybuilders: A qualitative investigation of facilitative psychosocial processes. Qualitative Research in Sport, Exercise, and Health. Advance online publication, doi 10.1080/2159676X.2013.766809). These analyses evidenced six MD mechanisms, and all three of the themes from Boardley and Grix (2013. Doping in bodybuilders: A qualitative investigation of facilitative psychosocial processes. Qualitative Research in Sport, Exercise, and Health. Advance online publication). Subsequent frequency analyses revealed six of the eight MD mechanisms, and two of the three additional themes, were common across the sample. Overall, the findings suggest MD may help athletes circumvent health- and morality-based deterrents to doping, describe a process linking supplement and PED use and detail how some athletes may actively avoid social censure for doping by only discussing PED use with other PED users from within their training environment.