Synthesis of human long-term metabolites of dehydrochloromethyltestosterone and oxymesterone

Kratena, Nicolas; Pfeffer, Sandra; Enev, Valentin S.; Gmeiner, Günter; Gärtner, Peter

doi:10.1016/j.steroids.2020.108716

“…In recent investigations the metabolite named "M3" in Sobolevsky's publication was assigned to 4α-chloro-17β-hydroxymethyl-17α-methyl-18-nor-5α-androst-13-en-3α-ol by comparison with synthesized reference material by Kratena et al [33]. Sobolevsky's "M4" was analogously assigned to 4-chloro-17αhydroxymethyl-17β-methyl-18-norandrosta-4,13-dien-3β-ol by our group in 2019 [26] and confirmed by Kratena et al [25]. The pathways of DHCMT metabolism are not fully uncovered yet, but due to the work of Liu et al and Stoll et al [27,29] some enzymes and metabolic processes came to the fore.…”

Section: Introductionsupporting

confidence: 65%

“…After the regioselective reduction of the 3-oxo group, the protection of the 3-hydroxy group followed and the intermediate was transformed using a method adapted from Kratena et al [25]. A new carbon-atom at position 17 was introduced.…”

Section: Metabolite Detectionmentioning

confidence: 99%

“…17β-Hydroxymethyl-17α-methyl-18-norandrost-13-ene metabolites of 17α-methyl steroids were first discovered in 2006, with the identification of a long-term metabolite of metandienone [16][17][18]. Subsequent research revealed analogous metabolites for other 17αmethyl steroids with capabilities for long-term detection, especially in case of oxandrolone and DHCMT [19][20][21][22][23][24][25][26][27]. As intermediates 17,17-dimethyl-18-norandrost-13-ene compounds are postulated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Controlled administration of dehydrochloromethyltestosterone in humans: Urinary excretion and long-term detection of metabolites for anti-doping purpose

Loke

¹

,

Torre

²

,

Iannone

³

et al. 2021

The Journal of Steroid Biochemistry and Molecular Biology

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“…In recent investigations the metabolite named "M3" in Sobolevsky's publication was assigned to 4α-chloro-17β-hydroxymethyl-17α-methyl-18-nor-5α-androst-13-en-3α-ol by comparison with synthesized reference material by Kratena et al [33]. Sobolevsky's "M4" was analogously assigned to 4-chloro-17αhydroxymethyl-17β-methyl-18-norandrosta-4,13-dien-3β-ol by our group in 2019 [26] and confirmed by Kratena et al [25]. The pathways of DHCMT metabolism are not fully uncovered yet, but due to the work of Liu et al and Stoll et al [27,29] some enzymes and metabolic processes came to the fore.…”

Section: Introductionsupporting

confidence: 64%

“…17β-Hydroxymethyl-17α-methyl-18-norandrost-13-ene metabolites of 17α-methyl steroids were first discovered in 2006, with the identification of a long-term metabolite of metandienone [16][17][18]. Subsequent research revealed analogous metabolites for other 17αmethyl steroids with capabilities for long-term detection, especially in case of oxandrolone and DHCMT [19][20][21][22][23][24][25][26][27]. As intermediates 17,17-dimethyl-18-norandrost-13-ene compounds are postulated.…”

Section: Introductionmentioning

confidence: 99%

Controlled Administration of Dehydrochloromethyltestosterone in Humans: Urinary Excretion and Long-Term Detection of Metabolites for Anti-Doping Purpose

Loke

¹

,

Torre

²

,

Iannone

³

et al. 2021

Preprint

0

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Dehydrochloromethyltestosterone (DHCMT) is an anabolic-androgenic steroid that was developed by Jenapharm in the 1960s and was marketed as Oral Turinabol. It is prohibited in sports at all times; nevertheless, there are several findings by anti-doping laboratories every year. New long-term metabolites have been proposed in 2011/12, which resulted in adverse analytical findings in retests of the Olympic games of 2008 and 2012. However, no controlled administration trial monitoring these long-term metabolites was reported until now. In this study, DHCMT (5 mg, p.o.) was administered to five healthy male volunteers and their urine samples were collected for a total of 60 days. The unconjugated and the glucuronidated fraction were analyzed separately by gas chromatography coupled to tandem mass spectrometry. The formation of the described long-term metabolites was verified, and their excretion monitored in detail. Due to interindividual differences there were several varieties in the excretion profiles among the volunteers. The metabolite M3, which has a fully reduced A-ring and modified D-ring structure, was identified by comparison with reference material as 4α- chloro-17β-hydroxymethyl-17α-methyl-18-nor-5α-androstan-13-en-3α-ol. It was found to be suitable as long-term marker for the intake of DHCMT in four of the volunteers. In one of the volunteers, it was detectable for 45 days after single oral dose administration. However, in two of the volunteers M5 (already published as long-term metabolite in the 1990s) showed longer detection windows. In one volunteer M3 was undetectable but another metabolite, M2, was found as the longest detectable metabolite. The last sample clearly identified as positive was collected between 9.9 and 44.9 days. Furthermore, the metabolite epiM4 (partially reduced A-ring and a modified D-ring structure which is epimerized in position 17 compared to M3) was identified in the urine of all volunteers with the help of chemically synthesized reference as 4-chloro-17α- hydroxymethyl-17β-methyl-18-nor-androsta-4,13-dien-3β-ol. It may serve as additional confirmatory metabolite. It is highly recommended to screen for all known metabolites in both fractions, glucuronidated and unconjugated, to improve identification of cheating athletes. This study also offers some deeper insights into the metabolism of DHCMT and of 17α- methyl steroids in general.

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