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The SG of the Sample, as determined by the Laboratory (see TD DL [5]); ii. |
The uncorrected concentrations of T, E, A, Etio, 5 αAdiol and 5βAdiol, and the T/E ratio; [Comment: When the ITP measurement of a steroid profile Marker is not possible due to, for example, dilution, unusual mat rix interferences, inhibition of the enzymatic hydrolysis or incomplete derivatization, the Laboratory should repeat the analysis with an alternative Sample preparation procedure (e.g. |
changing Aliquot volumes, application of solid phase extraction, or extraction with a different solvent). |
If, however, a Marker of the steroid profile cannot be quantified, the concentration of the affected Marker shall be reported as “ -1”. |
The Laboratory shall make a comment in the Test Report on why this Marker could not be quantified (e.g. |
< LOQ , incomplete derivatization). |
When the chromatographic peak signal for a Marker cannot be detected (i.e. |
is below the detection capability of the assay), the concentration of the Marker shall be repor ted as “ -2” (See Table 3 for reporting of specific situations for [T], [E], and T/E). |
The Laboratory may also provide information on other steroidal parameters such as prasterone (DHEA), dihydrotestosterone (DHT) and 6 α-hydroxy -androstenedione (6 α-OH-AD) at the request of the Testing Authority , Results Management Authority or the APMU .] |
iii. |
Any signs of microbial activity in the Sample , e.g. |
ratios of 5α -androstanedione (5α AND) to A and 5β -androstanedione (5βAND) to Etio, as determined from the respective steroid concentrations; iv. |
The presence or absence in the Sample of substance(s) that may alter the steroid profile (see Article 1.3). |
The Laboratory shall report the estimated levels of: • EtG if ≥ 5 µg/mL; • Carboxy -finasteride if ≥ 5 ng/mL; • 4-hydrox y- and/or 6 -hydroxy -dutasteride if ≥ 5 ng/mL; • Ketoconazole if ≥ 100 ng/mL; ABP Operating Guidelines – Version 9.0 – July 2023 Page 52/91 • Fluconazole if ≥ 500 ng/mL; • Miconazole if ≥ 1,000 ng/mL. |
2.2.1 Validity of the Sample Steroid Profile The validity of the Sample will be determined automatically upon reporting of the steroid profile in ADAMS. |
A Sample will be invalid only when the Sample shows signs of extensive degradation, as determined by: • 5αAND/A ≥ 0.1, and/or • 5βAND/Etio ≥ 0.1 [Comment: In addition, following the reporting of the steroid profile in ADAMS by the Laboratory , the Sample may be evaluated as “invalid” by the APMU upon review of the steroid profile data, for example, by considering the presence of substances that may alter the steroid profile in the Sample.] |
Table 3. |
Summary of conditions for reporting T and E concentrations and T/E ratio. |
Concentration of T Concentration of E T/E ratio Chromatographic peak signal of T measured at or above (≥) the LOQ . |
[T] ≥ LOQ (T) Report T as measured Chromatographic peak signal of E measured at or above (≥) LOQ . |
[E] ≥ LOQ (E) Report E as measured . |
Report T/E (as determined by the Laboratory from corrected peak heights/areas) Chromatographic peak signal of E detected, but below (<) LOQ . |
LOD (E) ≤ [E] < LOQ (E) Report E as “ -1” Chromatographic peak signal of E not detected. |
[E] < LOD (E) Report E as “ -2” Report T/E as “ -1” Report the LOD (E) Comment in ADAMS: T/E ratio could not be measured accurately because E could not be detected. |
Chromatographic peak signal of T detected, but below (<) the LOQ . |
LOD (T) ≤ [T] < LOQ (T) Report T as “ -1” Chromatographic peak signal of E measured at or above (≥) LOQ . |
[E] ≥ LOQ (E) Report E as measured Report T/E (as determined by the Laboratory from corrected peak heights/areas) Chromatographic peak signal of E detected, but below (<) LOQ . |
LOD (E) ≤ [E] < LOQ (E) Report E as “ -1” ABP Operating Guidelines – Version 9.0 – July 2023 Page 53/91 Chromatographic peak signal of E not detected. |
[E] < LOD (E) Report E as “ -2” Report T/E as “ -1” Comment in ADAMS: T/E ratio could not be measured accurately because the concentration of T could not be measured, and E could not be detected Chromatographic peak signal of T not detected. |
[T] < LOD (T) Report T as “ -2” Chromatographic peak signal of E measured at or above (≥) LOQ . |
[E] ≥ LOQ (E) Report E as measured Report T/E as “ -1” Report the LOD (T) Comment in ADAMS: T/E ratio could not be measured accurately because T could not be detected Chromatographic peak signal of E detected but below (<) LOQ . |
LOD (E) ≤ [E] < LOQ (E) Report E as “ -1” Report T/E as “ -1” Report the LOD (T) Comment in ADAMS: T/E ratio could not be measured because T could not be detected, and E could not be measured. |
Chromatographic peak signal of E not detected. |
[E] < LOD (E) Report E as “ -2” Report T/E as “ -2” Report the LOD (E) and LOD (T) Comment in ADAMS: T/E ratio could not be measured because T and E could not be detected . |
3.0 Confirmation Procedures (CP) The CP for the EAAS Markers include the GC -MSn (n ≥ 1) identification (in compliance with the TD IDCR [6]) and quantification, as well as the GC/C/IRMS analysis [7] of the Marker(s) of the steroid profile . |
In addition, the Laboratory shall confirm the presence or absence of factors impacting the steroid profile (see Article 1.3). |
3.1 CP Requests (CPRs) 3.1.1 CPRs triggered by Atypical Passport Findings (ATPF ) through ADAMS Once the Sample ’s steroid profile data are entered in ADAMS and matched with an Athlete , the Adaptive Model automatically updates the steroidal Passport. |
If an ATPF is identified based on an abnormally high T/E value, a CP request ( ATPF -CPR) is triggered and sent automatically to Laboratories through ADAMS. |
Upon receipt of an ATPF -CPR, the Laboratory shall proceed with the CP of the steroid profile as soon as possible, unless the presence of ethanol or other factors impacting the steroid profile has been detected in the Sample . |
In such cases, the Laboratory shall receive, within fifteen (15) days from the ABP Operating Guidelines – Version 9.0 – July 2023 Page 54/91 ATPF -CPR notification, an advice from the Passport Custodian or the Testing Authority (or Results Management Authority , if different ) on whether to proceed or not with the CP of the Sample ’s steroid profile. |
[Comment: In the absence of communication from the Passport Custodian or the Testing Authority (or Results Management Authority ) within fifteen (15) days from the ATPF -CPR notification, the Laboratory shall proceed with the CP of the steroid profile (see Article 3.2)]. |
Any justification from the Passport Custodian or the Testing Authority (or Results Management Authority ) not to proceed with the CP shall be provided in writing and in compliance with the TD APMU [8]. |
[Comment: I n cases when the Laboratory is instructed by the Passport Custodian or the Testing Authority (or Results Management Authority ) not to perform the CP, the Laboratory shall update the ADAMS Test Report for the Sample with a comment stating that the Passport Custodian, Testing Authority (or Results Management Authority ) requested not to perform the CP, and the reasons given.] |
When the Laboratory receives an ATPF -CPR for a Sample for which Adverse Analytical Finding(s) (AAF) have been reported for other Prohibited Substance(s) or Method(s) , the Laboratory shall consult the Testing Authority (or Results Management Authority , if different) about the need to conduct the CP for the Markers of the steroid profile. |
3.1.2 CPRs from the APMU , the Testing Authority (or Results Management Authority , as applicable) or WADA . |
The Adaptive Model will also determine abnormal values or sequences of the other ratios of the “steroid profile” (A/T, A/Etio, 5 αAdiol/5βAdiol, 5 αAdiol/E). |
However, in such cases the Laboratory will not receive an automatic “ ATPF -CPR” notification through ADAMS. |
Instead, the APMU will advise the Testing Authority (or Results Management Authority , if different ) on whether the Sample shall be subjected to CP . |
Therefore, in these cases the Laboratory shall receive a written request f rom the Testing Authority (or Results Management Authority , if different ) before proceeding with the CP . |
In the absence of an ATPF -CPR, requests for CP can be made also by the Testing Authority (or Results Management Authority , if different), the APMU *, or WADA . |
* where the respective client of the APMU has agreed to bestow such authority to the APMU . |
3.2 CP Test Methods 3.2.1 CP of Steroid Profile Markers by GC -MSn The Laboratory shall quantify all the Markers of the steroid profile in one Aliquot by a validated Fit -for-Purpose GC-MSn (n ≥ 1) quantification method. |
Identification (in compliance with the TD IDCR [6]) of the Markers that triggered the CP shall be performed as well. |
• In every case, the Laboratory shall confirm quantitatively all the Markers of the steroid profile before proceeding with the GC/C/IRMS analysis; [Comment: This requirement does not apply if the Testing Authority (or Results Management Authority , as applicable) has authorized the Laboratory to proceed directly to GC/C/IRMS analysis without a need for a quantitative confirmation of the steroid Markers (for example, in cases of limited Sample volume). |
ABP Operating Guidelines – Version 9.0 – July 2023 Page 55/91 For T/E values, only T needs to be confirmed if E is not detected or the volume of the Sample is not sufficient.] |
• In the case of an ATPF -CPR for an abnormally high T/E ratio, GC/C/IRMS analysis is not mandatory when the confirmed T/E value is below the confirmation T/E cut -off calculated by the Adaptive Model and provided within the ATPF -CPR notification received from ADAMS; • For other CP requests, when the steroid profile CP does not confirm the ITP values that triggered the CP (e.g. |
5αAdiol/E value), taking into consideration the expanded uncertainty of the measurement ( U95%, k = 2), the Laboratory shall consult the Testing Authority to determine if the GC/C/IRMS analysis is necessary. |
In the event that GC/C/IRMS analysis is deemed unnecessary, the Laboratory shall update the ADAMS report for the Sample with the confirmed values of all the Markers of the steroid profile and include a comment that GC/C/IRMS analysis was not necessary. |
[Comment: for ratios other than the T/E, the uc (%) of the ratio shall be calculated by propagation of uncertainties of the corresponding Marker concentrations.] |
The same analytical requirements presented in Table 2 for the ITP shall apply for the GC -MSn CP, with the following modifications: • GC-MSn CP Validation Requirements - For determinations of A, Etio, 5α Adiol and 5β Adiol, the uc (%) shall be not greater than (≤) 15% when the concentrations are five times (5x) the respective LOQ ; - For determinations of T, E and T/E ratios, the u c (%) shall be not greater than (≤) 15% when the concentrations of T and E are greater than (>) 5 ng/mL . |
• GC-MSn CP Analysis Requirements - A Solid Phase Extraction (SPE) shall be performed prior to the enzymatic hydrolysis of the Sample; - Calibration standard(s) and at least two (2) QC urine samples containing representative low and high levels of the Marker s of the steroid profile shall be included. |
3.2.2 GC/C/IRMS CP Technical and reporting requirements for the GC/C/IRMS CP are specified in the TD IRMS [7]. |
When an AAF is reported for the Marker (s) of the steroid profile based on the results of a GC/C/IRMS analysis performed on the “A” Sample , only the GC/C/IRMS analysis, including the identification of the relevant Markers (target compounds and endogenous reference compounds) shall be repeated during the “B” Sample CP. |
3.3 Reporting Results from the CP 3.3.1 “A” Sample Following the CP performed for the steroid profile on the “A” Sample , the Laboratory shall report in ADAMS: ABP Operating Guidelines – Version 9.0 – July 2023 Page 56/91 i. |
The SG of the Sample (determined from a new Aliquot of the “A” Sample) ; ii. |
The confirmed value of the Markers of the steroid profile (concentrations, T/E value), without adjustment for the SG of the Sample ; iii. |
The associated u c (expressed in units); iv. |
The GC/C/IRMS confirmation results, if performed (see TD IRMS [7]). |
The Laboratory shall update the Test Report for the Sample in ADAMS (as AAF, Atypical Finding (ATF), or Negative Finding) based on the results of the GC/C/IRMS CP; v. The confirmed results (presence/absence) for signs of microbial activity: 5 αAND/A, 5βAND/Etio, and T free/Ttotal; based on concentrations; [Comment : In addition to the determination of the 5 αAND/A and 5βAND/Etio ratios as signs of microbial contamination, the determination during the CP of an elevated ratio of free Testosterone to total Testosterone (T free / Ttotal > 0.05) will also invalidate (the steroid profile of) the Sample. |
However, this shall not preclude the performance of the GC/C/I RMS CP or invalidate its results.] |
vi. |
The presence or absence in the Sample of substance(s) that do not constitute an AAF but may alter the steroid profile (see Article 1.3): if detected in the Sample, the Laboratory shall report the confirmed estimated levels of EtG, 5α -reductase inhibitors and -azoles as specified in Article 2.2 (without the need to report the u c for these determinations). |
3.3.2 “B” Sample Following the performance of the GC/C/IRMS CP for the steroid profile on the “B” Sample , the Labo ratory shall report the GC/C/IRMS confirmation results (see TD IRMS [7]) in ADAMS. |
[Comment: If the Sample has not been reported as an AAF for the Marker(s) of the steroid profile based on the results of the GC/C/IRMS analysis, but the steroid profile CP by GC -MSn has been requested for the “B” Sample, then the Laboratory shall report in ADAMS the results of the “B” confirmation of the steroid profile as described for the “A” Sample in Article 3.3.1.] |
4.0 Reporting Sample Manipulation ( Tampering or Attempted Tampering) Tampering or Attempted Tampering aims to alter the integrity and validity of Samples collected during Doping Control , including, but not limited to Sample substitution with another fluid and urine exchange and/or adulteration ( e.g. |
addition of proteases to Sample) . |
[Comment: the substitu tion of an Athlete’s urine Sample with the urine of another individual (urine exchange) can be uncovered using the steroidal Passport and confirmed by DNA analysis across multiple Samples, as described in the TD APMU [8].] |
In cases when a Sample is not consistent with human urine ( e.g. |
SG ≤ 1.001, creatinine ≤ 5 mg/dL [9], non-physiological salt concentration, abnormal pH values, absence or abnormally low levels of endogenous steroids, corticosteroids, proteins, etc. |
), the Laboratory shall: i. |
Report the fi nding as an AAF for Tampering or Attempted Tampering (class M2.1 of the Prohibited List ) if the Laboratory can determine the general nature/type of the adulterated Sample, which is not consistent with human urine ( e.g. |
water, liquor, synthetic urine) ; OR ABP Operating Guidelines – Version 9.0 – July 2023 Page 57/91 ii. |
Report the finding as an ATF for Tampering or Attempted Tampering and include a comment in ADAMS advising the Testing Authority to perform further investigations ( e.g. |
additional analyses on the Sample, Target Testing the Athlete ). |
5.0 References [1] Mareck U et al . |
Factors influencing the steroid profile in doping control analysis. |
J Mass Spectrom. |
43(7):877- 91, 2008. |
[2] Ayotte C. Detecting the administration of endogenous anabolic androgenic steroids. |
Handb Exp Pharmacol. |
195:77- 98, 2010. |
[3] Kuuranne T, Saugy M, Baume N . |
Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling. |
Br J Sports Med . |
48(10): 848- 55, 2014. |
[4] The World Anti -Doping Code International Standard for Results Management . |
[5] WADA Technical Document TD DL: Decision Limits for the Confirmatory Quantification of Exogenous Threshold Substances by Chromatography -based Analytical Methods . |
[6] WADA Technical Document TD IDCR: Minimum Criteria for Chromatographic -Mass Spectrometric Confirmation of the Identity of Analy tes for Doping Control Purposes. |
[7] WADA Technical Document TD IRMS: Detection of Synthetic Forms of Prohibited Substances by GC/C/IRMS. |
[8] WADA Technical Document TD APMU: Athlete Passport Management Unit – Requirements and Procedures. |
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