PMID- 34648228 OWN - NLM STAT- MEDLINE DCOM- 20220316 LR - 20220316 IS - 1942-7611 (Electronic) IS - 1942-7603 (Linking) VI - 13 IP - 11-12 DP - 2021 Nov TI - Sensitive detection of testosterone and testosterone prohormone administrations based on urinary concentrations and carbon isotope ratios of androsterone and etiocholanolone. PG - 1835-1851 LID - 10.1002/dta.3168 [doi] AB - The testing strategy for the detection of testosterone (T) or T-prohormones is based on the longitudinal evaluation of urinary steroid concentrations accompanied by subsequent isotope ratio mass spectrometry (IRMS)-based confirmation of samples showing atypical concentrations or concentration ratios. In recent years, the IRMS methodology focussed more and more on T itself and on the metabolites of T, 5alpha- and 5beta-androstanediol. These target analytes showed the best sensitivity and retrospectivity, but their use has occasionally been challenging due to their comparably low urinary concentrations. Conversely, the carbon isotope ratios (CIR) of the main urinary metabolites of T, androsterone (A) and etiocholanolone (EITO), can readily be measured even from low urine volumes; those however, commonly offer a lower sensitivity and shorter retrospectivity in uncovering T misuse. Within this study, the CIRs of A and ETIO were combined with their urinary concentrations, resulting in a single parameter referred to as 'difference from weighted mean' (DWM). Both glucuronidated and sulfated steroids were investigated, encompassing a reference population (n = 110), longitudinal studies on three individuals, influence of ethanol in two individuals, and re-analysis of several administration studies including T, dihydrotestosterone, androstenedione, epiandrosterone, dehydroepiandrosterone, and T-gel. Especially DWM calculated for the sulfoconjugated steroids significantly prolonged the detection time of steroid hormone administrations when individual reference ranges were applied. Administration studies employing T encompassing CIR common for Europe (-23.8 per thousand and -24.4 per thousand) were investigated and, even though for a significantly shorter time period and less pronounced, DWM could demonstrate the exogenous source of T metabolites. CI - (c) 2021 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 - Haenelt, Nadine AU - Haenelt N AD - Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Koln, Germany. FAU - Fussholler, Gregor AU - Fussholler G AD - Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Koln, Germany. FAU - Geyer, Hans AU - Geyer H 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 - Federal Ministry of the Interior, Building and Community/ GR - Manfred-Donike Institute for Doping Analysis/ PT - Journal Article DEP - 20211021 PL - England TA - Drug Test Anal JT - Drug testing and analysis JID - 101483449 RN - 0 (Carbon Isotopes) RN - 0 (Testosterone Congeners) RN - 3K9958V90M (Ethanol) RN - 3XMK78S47O (Testosterone) RN - 97CGB1M48I (Etiocholanolone) RN - C24W7J5D5R (Androsterone) SB - IM MH - Androsterone/*analysis/urine MH - Carbon Isotopes MH - Doping in Sports/prevention & control MH - Ethanol/administration & dosage/pharmacology MH - Etiocholanolone/*analysis/urine MH - Female MH - Humans MH - Longitudinal Studies MH - Male MH - Mass Spectrometry/methods MH - Middle Aged MH - Substance Abuse Detection/methods MH - Testosterone/*analysis/urine MH - Testosterone Congeners/*analysis/urine OTO - NOTNLM OT - doping OT - endogenous carbon isotope ratios OT - isotope ratio mass spectrometry OT - steroid concentrations OT - testosterone EDAT- 2021/10/15 06:00 MHDA- 2022/03/17 06:00 CRDT- 2021/10/14 12:33 PHST- 2021/09/06 00:00 [revised] PHST- 2021/07/22 00:00 [received] PHST- 2021/09/16 00:00 [accepted] PHST- 2021/10/15 06:00 [pubmed] PHST- 2022/03/17 06:00 [medline] PHST- 2021/10/14 12:33 [entrez] AID - 10.1002/dta.3168 [doi] PST - ppublish SO - Drug Test Anal. 2021 Nov;13(11-12):1835-1851. doi: 10.1002/dta.3168. Epub 2021 Oct 21.