PMID- 36001066
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221222
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Linking)
VI  - 14
IP  - 11-12
DP  - 2022 Nov
TI  - Addressing recent challenges in isotope ratio mass spectrometry: Development of a 
      method applicable to 1-androstene-steroids, 6alpha-hydroxy-androstenedione, and 
      androstatrienedione.
PG  - 1891-1903
LID - 10.1002/dta.3361 [doi]
AB  - In 2020, the confirmation of the non-endogenous origin of several 
      pseudo-endogenous steroids by means of isotope ratio mass spectrometry (IRMS) was 
      recommended by the World Anti-Doping Agency (WADA), in addition to previously 
      established target analytes for IRMS in sports drug testing. To date, however, 
      IRMS-based methods validated in accordance with current WADA regulations have not 
      been available. Therefore, the aim of this research project was the development 
      and validation of a method to determine the carbon isotope ratios (CIR) of all 
      newly considered pseudo-endogenous steroids, encompassing the anabolic androgenic 
      steroids comprising a 1-ene-core structure (5alpha-androst-1-ene-3beta,17beta-diol, 
      5alpha-androst-1-ene-3,17-dione [1AD], 17beta-hydroxy-5alpha-androst-1-en-3-one, 
      3alpha-hydroxy-5alpha-androst-1-ene-17-one [1AND], and 3beta-hydroxy-5alpha-androst-1-ene-17-one 
      [1EpiAND]), as well as steroids referred to as hormone and metabolic modulators 
      (androsta-1,4,6-triene-3,17-dione [TRD] and its main metabolite 
      17beta-hydroxy-androsta-1,4,6-triene-3-one) and 6alpha- and 
      6beta-hydroxy-androst-4-ene-3,17-dione. With peak purity of target analytes being 
      critical for IRMS analyses, a twofold high-performance liquid chromatography 
      (HPLC)-based sample purification was employed, with all analytes being acetylated 
      between the first and second HPLC fractionation. Using established gas 
      chromatography/combustion/IRMS instrumentation, limits of quantification were 
      estimated at 10 ng/ml for a 20 ml urine aliquot for all analytes, except for 1AND 
      (20 ng/ml), and combined measurement uncertainties were estimated between 0.4 per thousand 
      and 0.9 per thousand. For proof-of-concept, samples collected after the single oral 
      administration of a nutritional supplement containing 1AD and 1EpiAND were 
      analyzed as well as existing excretion study urine samples obtained after the 
      administration of 4-androstenedione and TRD. Based on the obtained results, the 
      developed method was considered to be fit-for-purpose.
CI  - (c) 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
FAU - Piper, Thomas
AU  - Piper T
AUID- ORCID: 0000-0002-7462-6693
AD  - Center for Preventive Doping Research - Institute of Biochemistry, German Sport 
      University Cologne, Koln, Germany.
FAU - Thevis, Mario
AU  - Thevis M
AUID- ORCID: 0000-0002-1535-6451
AD  - Center for Preventive Doping Research - Institute of Biochemistry, German Sport 
      University Cologne, Koln, Germany.
AD  - European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, 
      Germany.
LA  - eng
GR  - Bundesministerium des Innern, fur Bau und Heimat/
GR  - Manfred-Donike Institute for Doping Analysis/
GR  - 20A07MT/World Anti-Doping Agency/
PT  - Journal Article
DEP - 20220831
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 409J2J96VR (Androstenedione)
RN  - 0 (Steroids)
RN  - 0 (Carbon Isotopes)
SB  - IM
MH  - *Androstenedione
MH  - Steroids/urine
MH  - Gas Chromatography-Mass Spectrometry/methods
MH  - Substance Abuse Detection/methods
MH  - Carbon Isotopes
MH  - *Doping in Sports
OTO - NOTNLM
OT  - 1-testosterone
OT  - androstatrienedione
OT  - carbon isotope ratios
OT  - doping controls
OT  - isotope ratio mass spectrometry
EDAT- 2022/08/25 06:00
MHDA- 2022/12/17 06:00
CRDT- 2022/08/24 10:43
PHST- 2022/08/18 00:00 [revised]
PHST- 2022/07/04 00:00 [received]
PHST- 2022/08/19 00:00 [accepted]
PHST- 2022/08/25 06:00 [pubmed]
PHST- 2022/12/17 06:00 [medline]
PHST- 2022/08/24 10:43 [entrez]
AID - 10.1002/dta.3361 [doi]
PST - ppublish
SO  - Drug Test Anal. 2022 Nov;14(11-12):1891-1903. doi: 10.1002/dta.3361. Epub 2022 
      Aug 31.