Annual Report 2019 / Kazakhstan National Anti-Doping Centre (KazNADC). - Almaty : KazNADC, 2020

Annual Report 2020 / Kazakhstan National Anti-Doping Centre (KazNADC). - Almaty : KazNADC, 2021

Annual Report 2021 / Kazakhstan National Anti-Doping Centre (KazNADC). - Almaty : KazNADC, 2022

Meldonium residues in milk : A possible scenario for inadvertent doping in sports? / Sven Guddat, Christian Görgens, Tim Sobolevsky, Mario Thevis. - (Drug Testing and Analysis (2021) 26 August)

• PMID: 34448364
• DOI: 10.1002/dta.3145

Abstract

Lately, the veterinary drug Emidonol® has been discussed as a possible scenario for inadvertent doping in sports. Emidonol® is approved for use in livestock breeding, exhibiting antihypoxic and weak sedative effects. The veterinary drug rapidly dissociates into meldonium, a substance prohibited in sports, and is excreted largely in its unchanged form into urine. To investigate if residues of meldonium in edible produce may result in adverse analytical findings in sports drug testing, a pilot study was conducted with three volunteers consuming a single dose of 100 ml meldonium-spiked milk at a concentration of 500 ng/ml (Study 1), and multiple doses of 100 ml of meldonium-spiked milk (500 ng/ml) on five consecutive days (Study 2). In the single dose study, urinary meldonium concentrations peaked between 2 and 6 h post-administration with maximum values of 7.5 ng/ml, whereas maximum meldonium concentrations of 18.6 ng/ml were determined after multiple doses 4 h post-administration. All samples were analyzed using an established and validated protocol based on HILIC-HRMS/MS.

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).

Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements / Donata Favretto, Sindi Visentin Salvatore Scrivano, Emanuele Roselli, Fabio Mattiazzi, Roberto Pertile, Susanna Vogliardi, Marianna Tucci, Massimo Montisci. - (Drug Testing and Analysis 11(2018) 3 (March) ; 512-522)

• PMID: 30194914.
• DOI: 10.1002/dta.2499

Abstract

Diuretic agents are prohibited in sports in- and out-of-competition according to the regulations of the World Anti-Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (μg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA-accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy. His nutritional supplements were analyzed revealing HCTZ presence in different concentrations, at the ppm level (μg/g and ng/mL). With the aim of testing the plausibility of the observed urinary HCTZ concentrations with the nutritional supplement ingestion, a urinary excretion study with three healthy volunteers was performed. HCTZ-contaminated powder (6.4 μg/g of HCTZ) was administered to each subject in different dosages, reproducing the possible ingestion pattern occurred. Urine specimens were collected before and after ingestion of the powder, up to 24 hours, and underwent liquid-liquid extraction and liquid chromatography-tandem mass spectrometry determination. Post-administration specimens were found to contain HCTZ at concentrations of 5-230 ng/mL, which supported the accidental inadvertent intake of the prohibited substance by the athlete. This study makes the argument that the introduction of reporting limits for diuretics are warranted in doping control samples, in order to protect against inadvertent AAFs due to contaminated products.

NADA Annual Report 2016 / Nationale Anti Doping Agentur Deutschland (NADA). - Bonn : NADA, 2017

• NADA Material No. 63

NADA Annual Report 2017 / National Anti Doping Agency of Germany. - Bonn : Nationale Anti Doping Agentur Deutschland (NADA), 2018
NADA Material No. 63