WADA releases Laboratory Technical Letters for 2021

The World Anti-Doping Agency (WADA) publishes today the following Technical Letters (TLs) for 2021 and the Summary of Modifications which were approved by WADA’s Executive Committee, via circulatory vote, on 21 December 2020.

This particular review of WADA’s TLs was triggered by the need to bring the below TLs in line with the 2021 World Anti-Doping Code (Code) and the 2021 International Standard for Laboratories (ISL) which both come into force on 1 January 2021.

Under the ISL, WADA’s TLs provide specific instructions to the WADA-accredited Laboratories, WADA-approved Laboratories and other stakeholders regarding the analysis, interpretation and reporting of results for particular Prohibited Substance(s) and/or Prohibited Method(s), or the application of specific laboratory procedures. As part of WADA’s mandate to enhance anti-doping activities under the Code, TLs undergo periodic revisions to reflect scientific and technological advances in the performance of anti-doping tests and the reporting of test results. They are refined and revised in consultation with WADA stakeholders.

2021 TECHNICAL LETTERS

1. TL01 – Meclofenoxate

In this new version of the TL, an explanatory comment regarding the pharmacokinetics of CPAHs herbicides was included in the introduction, and reporting levels of meclofenoxate and 4-CPA are now provided in the section related to Analysis and Reporting Requirements. Additional guidance for the “B” Confirmation Procedure was included. Terms and definitions have been updated where relevant.

2. TL02 – Mebeverine Metabolism

In this new version of the TL, two mebeverine-specific Metabolites have been specified (mebeverine acid and desmethyl mebeverine acid), replacing the p-methoxy-ethylamphetamine, p-OH-ethylamphetamine and p-methoxy-amphetamine metabolites, which have been removed from the Reporting Requirements. Terms and definitions have been updated where relevant.

3. TL03 – Zilpaterol

In this new version of the TL, articles have been reorganized to facilitate interpretation. Terms and definitions have been updated where relevant.

4. TL04 – Zeranol

In this new version of the TL, articles have been reorganized to facilitate interpretation. Terms and definitions have been updated where relevant.

5. TL05 – Oxilofrine

In this new version of the TL, additional analysis and requirements were included to address whether the oxilofrine finding is consistent with the metabolization of ephedrine. Therefore, a specific minimum reporting level has been established for oxilofrine when detected in the presence of ephedrine. Terms and definitions have been updated where relevant.

6. TL06 – Possible Metabolism of Proguanil into Chlorazanil

 In this new version of the TL, articles have been reorganized to facilitate interpretation. The “Scientific Background” information has been removed, and the relevant information moved into the Introduction article. A scientific publication regarding the formation of the diuretic chlorazanil from the antimalarial drug proguanil has been included as a reference. Other terms and definitions have been updated where relevant.

7. TL07 – Andarine – Flutamide

In this new version of the TL, the Analysis and Reporting requirements have been updated to clarify the specific case for which an Adverse Analytical Finding (AAF) for andarine shall be reported. In addition, a comment specifying that the Laboratories shall not report an AAF for andarine based only on the presence of O-dephenylandarine has been included. Terms and definitions have been updated where relevant.

8. TL08 – Use of Internal Standards

In this new version of the TL, articles have been reorganized to facilitate interpretation. Terms and definitions have been updated where relevant.

9. TL09 – Oxethazaine

In this new version of the TL, articles have been reorganized to facilitate interpretation. Terms and definitions have been updated where relevant.

10. TL10 – In situ Formation of Exogenous Compounds

In this new version of the TL, the requirements regarding prednisolone and prednisone analysis have been removed. Terms and definitions have been updated where relevant.

11. TL11 – Oxymorphone

In this new version of the TL, the Reporting Requirements now include the mandatory analysis of methylnatrexone by LC-MS before reporting an AAF for oxymorphone. Terms and definitions have been updated where relevant.

12. TL12 – Enobosarm

In this new version of the TL, the TL name has been updated from “TL12 – Ostarine” to “TL12 – Enobosarm” to be aligned with the Selective Androgen Receptor Modulators’ (SARMs) nomenclature used in the Prohibited List. The Analysis and Reporting requirements have been updated to clarify the specific case for which an enobosarm AAF shall be reported. In addition, a comment was included specifying that the Laboratories shall not report an AAF for enobosarm based only on the presence of O-dephenylandarine. Terms and definitions have been updated where relevant.

13. TL13 – Trimetazidine

In this new version of the TL, the Analysis and Reporting Requirements article includes additional guidance that the Laboratories shall consider before reporting an AAF for trimetazidine. Therefore, the instruction to consult the WADA Science Department for trimetazidine suspicious findings has been removed. Terms and definitions have been updated where relevant.

14. TL14 – Difference in “A” and “B” Sample Urine Characteristics

In this new version of the TL, terms and definitions have been updated where relevant.

15. TL15 – Hydromorphone

In this new version of the TL, terms and definitions have been updated where relevant.

16. TL16 – Tretoquinol

In this new version of the TL, the instruction to report an AAF for tretoquinol only if the sample has been collected after 15 January 2019 has been removed. In addition, the instruction to record samples in which the tretoquinol concentration is estimated below 20 ng/mL has been also removed. Terms and definitions have been updated where relevant.
 

17. TL17 – Detection of Tulobuterol in the Presence of Bupropion

In this new version of the TL, relevant articles have been reorganized to facilitate interpretation. Terms and definitions have been updated where relevant.

18. TL18 – Testolactone

In this new version of the TL, terms and definitions have been updated where relevant.

19. TL19 – Prednisone and Prednisolone

In this new version of the TL, updates were necessary to align the TL with the new TD2021IRMS. The reference to TL10 has been removed from the Introduction and updates have been made on terms and definitions, where relevant, for consistency with the TD2021IRMS.

20. TL20 – Specific Substances with a Steroid Structure

In this new version of the TL, additional substances have been included, which the Laboratories shall consider before reporting a result as an AAF. In addition, since the new TD2021IRMS does not include specific criteria for the GC/C/IRMS analysis of the substances mentioned in this TL, the recommendation to perform GC/C/IRMS analysis has been removed. Terms and definitions have been updated where relevant.

21. TL21 – 6-oxo and Metabolites

In this new version of the TL, terms and definitions have been updated where relevant.

22. TL22 – Ethylmorphine

In this new version of the TL, the WADA Laboratory Expert Group (LabEG) proposed to postpone the effective date of the TL22 until 1 May 2021 due to the lack of commercial sources of the norethylmorphine reference material. Several sources for the reference material have been identified and availability is expected soon. WADA is monitoring these efforts.

DEADLINES

Please note that all WADA-accredited Laboratories are required to implement these TLs in their procedures by the following deadlines:

1 January 2021:

• TL01 – Meclofenoxate
• TL03 – Zilpaterol
• TL04 – Zeranol
• TL06 – Possible Metabolism of Proguanil into Chlorazanil
• TL07 – Andarine – Flutamide
• TL08 – Use of Internal Standards
• TL09 – Oxethazaine
• TL10 – In Situ Formation of Exogenous Compounds
• TL12 – Enobosarm
• TL13 – Trimetazidine
• TL14 – Difference in “A” and “B” Sample Urine Characteristics
• TL15 – Hydromorphone
• TL16 – Tretroquinol
• TL17 – Detection of Tulobuterol in the Presence of Bupropion
• TL18 – Testolactone
• TL19 – Prednisone and Prednisolone
• TL20 – Specific Substances with a Steroid Structure
• TL21 – 6-oxo and metabolites

1 April 2021:

• TL02 – Mebeverine Metabolism
• TL05 – Oxilofrine
• TL11 – Oxymorphone

1 May 2021:

• TL22 – Ethylmorphine

The above TLs are available and indexed on WADA’s website.

Should you have any questions or comments regarding the 2021 Technical Letters, please feel free to contact WADA’s Science Department at: science@wada-ama.org.