Studies on the in vivo metabolism of methylstenbolone and detection of novel long term metabolites for doping control analysis

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Studies on the in vivo metabolism of methylstenbolone and detection of novel long term metabolites for doping control analysis. / Piper, Thomas; Fusshöller, Gregor; Schänzer, Wilhelm et al.

in: Drug testing and analysis, Jahrgang 11, Nr. 11-12, 01.11.2019, S. 1644-1655.

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@article{60e7225a6e4a48469f54e694cb307daa,
title = "Studies on the in vivo metabolism of methylstenbolone and detection of novel long term metabolites for doping control analysis",
abstract = "Abstract The anabolic-androgenic steroid methylstenbolone (MSTEN; 2α,17α-dimethyl-17β-hydroxy-5α-androst-1-en-3-one) is available as a so-called designer steroid or nutritional supplement. It is occasionally detected in doping control samples, predominantly tested and confirmed as the glucuronic acid conjugate of methylstenbolone. The absence of other meaningful metabolites reported as target analytes for sports drug testing purposes can be explained by the advertised metabolic stability of methylstenbolone. In 2013, a first investigation into the human metabolism of methylstenbolone was published, and two hydroxylated metabolites were identified as potential targets for initial testing procedures in doping controls. These metabolites were not observed in recent doping control samples that yielded adverse analytical findings for methylstenbolone, and in the light of additional data originating from a recent publication on the in vivo metabolism of methylstenbolone in the horse, revisiting the metabolic reactions in humans appeared warranted. Therefore, deuterated methylstenbolone together with hydrogen isotope ratio mass spectrometry (IRMS) in combination with high accuracy/high resolution mass spectrometry were employed. After oral administration of a single dose of 10 mg of doubly labeled methylstenbolone, urine samples were collected for 29 days. Up to 40 different deuterated methylstenbolone metabolites were detected in post-administration samples, predominantly as glucuronic acid conjugates, and all were investigated regarding their potential to prolong the detection window for doping controls. Besides methylstenbolone excreted glucuronidated, three additional metabolites were still detectable at the end of the study on day 29. The most promising candidates for inclusion into routine sports drug testing methods (2α,17α-dimethyl-5α-androst-1-ene-3β,17β-diol and 2α,17α-dimethyl-5α-androst-1-ene-3α,17β-diol) were synthesized and characterized by NMR.",
keywords = "doping control, high resolution-high accuracy mass spectrometry, human metabolism, hydrogen isotope ratio mass spectrometry, methylstenbolone",
author = "Thomas Piper and Gregor Fussh{\"o}ller and Wilhelm Sch{\"a}nzer and Andreas Lagojda and Dirk Kuehne and Mario Thevis",
year = "2019",
month = nov,
day = "1",
doi = "10.1002/dta.2736",
language = "English",
volume = "11",
pages = "1644--1655",
journal = "Drug testing and analysis",
issn = "1942-7603",
publisher = "John Wiley & Sons, Ltd",
number = "11-12",
note = "Manfred Donike Workshop on Doping Analysis ; Conference date: 17-02-2019 Through 22-02-2019",

}

RIS

TY - JOUR

T1 - Studies on the in vivo metabolism of methylstenbolone and detection of novel long term metabolites for doping control analysis

AU - Piper, Thomas

AU - Fusshöller, Gregor

AU - Schänzer, Wilhelm

AU - Lagojda, Andreas

AU - Kuehne, Dirk

AU - Thevis, Mario

N1 - Conference code: 37

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Abstract The anabolic-androgenic steroid methylstenbolone (MSTEN; 2α,17α-dimethyl-17β-hydroxy-5α-androst-1-en-3-one) is available as a so-called designer steroid or nutritional supplement. It is occasionally detected in doping control samples, predominantly tested and confirmed as the glucuronic acid conjugate of methylstenbolone. The absence of other meaningful metabolites reported as target analytes for sports drug testing purposes can be explained by the advertised metabolic stability of methylstenbolone. In 2013, a first investigation into the human metabolism of methylstenbolone was published, and two hydroxylated metabolites were identified as potential targets for initial testing procedures in doping controls. These metabolites were not observed in recent doping control samples that yielded adverse analytical findings for methylstenbolone, and in the light of additional data originating from a recent publication on the in vivo metabolism of methylstenbolone in the horse, revisiting the metabolic reactions in humans appeared warranted. Therefore, deuterated methylstenbolone together with hydrogen isotope ratio mass spectrometry (IRMS) in combination with high accuracy/high resolution mass spectrometry were employed. After oral administration of a single dose of 10 mg of doubly labeled methylstenbolone, urine samples were collected for 29 days. Up to 40 different deuterated methylstenbolone metabolites were detected in post-administration samples, predominantly as glucuronic acid conjugates, and all were investigated regarding their potential to prolong the detection window for doping controls. Besides methylstenbolone excreted glucuronidated, three additional metabolites were still detectable at the end of the study on day 29. The most promising candidates for inclusion into routine sports drug testing methods (2α,17α-dimethyl-5α-androst-1-ene-3β,17β-diol and 2α,17α-dimethyl-5α-androst-1-ene-3α,17β-diol) were synthesized and characterized by NMR.

AB - Abstract The anabolic-androgenic steroid methylstenbolone (MSTEN; 2α,17α-dimethyl-17β-hydroxy-5α-androst-1-en-3-one) is available as a so-called designer steroid or nutritional supplement. It is occasionally detected in doping control samples, predominantly tested and confirmed as the glucuronic acid conjugate of methylstenbolone. The absence of other meaningful metabolites reported as target analytes for sports drug testing purposes can be explained by the advertised metabolic stability of methylstenbolone. In 2013, a first investigation into the human metabolism of methylstenbolone was published, and two hydroxylated metabolites were identified as potential targets for initial testing procedures in doping controls. These metabolites were not observed in recent doping control samples that yielded adverse analytical findings for methylstenbolone, and in the light of additional data originating from a recent publication on the in vivo metabolism of methylstenbolone in the horse, revisiting the metabolic reactions in humans appeared warranted. Therefore, deuterated methylstenbolone together with hydrogen isotope ratio mass spectrometry (IRMS) in combination with high accuracy/high resolution mass spectrometry were employed. After oral administration of a single dose of 10 mg of doubly labeled methylstenbolone, urine samples were collected for 29 days. Up to 40 different deuterated methylstenbolone metabolites were detected in post-administration samples, predominantly as glucuronic acid conjugates, and all were investigated regarding their potential to prolong the detection window for doping controls. Besides methylstenbolone excreted glucuronidated, three additional metabolites were still detectable at the end of the study on day 29. The most promising candidates for inclusion into routine sports drug testing methods (2α,17α-dimethyl-5α-androst-1-ene-3β,17β-diol and 2α,17α-dimethyl-5α-androst-1-ene-3α,17β-diol) were synthesized and characterized by NMR.

KW - doping control

KW - high resolution-high accuracy mass spectrometry

KW - human metabolism

KW - hydrogen isotope ratio mass spectrometry

KW - methylstenbolone

UR - https://www.mendeley.com/catalogue/b500520f-13d8-3b5b-b23e-aa692f8fbc0a/

U2 - 10.1002/dta.2736

DO - 10.1002/dta.2736

M3 - Conference article in journal

VL - 11

SP - 1644

EP - 1655

JO - Drug testing and analysis

JF - Drug testing and analysis

SN - 1942-7603

IS - 11-12

T2 - Manfred Donike Workshop on Doping Analysis

Y2 - 17 February 2019 through 22 February 2019

ER -

ID: 5183476