In vivo metabolism of Δ, 17α-methyltestosterone in man

Rongone, Edward L.; Segaloff, Albert

doi:10.1016/s0039-128x(63)80135-x

Cited by 40 publications

(8 citation statements)

References 7 publications

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“…[8] Based on the common ionization and collision-induced dissociation (CID) behaviour of steroid glucuronides, [16] a series of open detection methods based on neutral loss (NL) and precursor ion (PI) scan have been proposed to detect them by LC-MS/MS. [2,3,5,6,12,[18][19][20][21][22][23][24] The most important metabolites are glucuronoconjugates that have been studied using β-glucuronidase hydrolysis. [11,12,17] Metandienone (MTD) is one of the most frequently detected AAS, and its metabolism has been widely studied.…”

Section: Introductionmentioning

confidence: 99%

“…[8] Selected reaction monitoring (SRM) methods using characteristic ion transitions of potential steroid phase II metabolites have been also used in previous works to detect new phase II metabolites. [18] As indicated above, β-glucuronidase resistant metabolites, containing a 6β-hydroxy group have been recently described for testosterone. [2,3,5,6,12,[18][19][20][21][22][23][24] The most important metabolites are glucuronoconjugates that have been studied using β-glucuronidase hydrolysis.…”

Section: Introductionmentioning

confidence: 99%

“…[11,12,17] Metandienone (MTD) is one of the most frequently detected AAS, and its metabolism has been widely studied. [2,3,5,6,12,[18][19][20][21][22][23][24] The most important metabolites are glucuronoconjugates that have been studied using β-glucuronidase hydrolysis. Another important metabolite is 6β-hydroxy-MTD, detected in free form.…”

Section: Introductionmentioning

confidence: 99%

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LC‐MS/MS detection of unaltered glucuronoconjugated metabolites of metandienone

Esquivel

Pozo

Garrostas

et al. 2016

Drug Testing and Analysis

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The aim of this study was to evaluate the direct detection of glucuronoconjugated metabolites of metandienone (MTD) and their detection times. Metabolites resistant to enzymatic hydrolysis were also evaluated. Based on the common mass spectrometric behaviour of steroid glucuronides, three liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategies were applied for the detection of unpredicted and predicted metabolites: precursor ion scan (PI), neutral loss scan (NL), and theoretical selected reaction monitoring (SRM) methods. Samples from four excretion studies of MTD were analyzed for both the detection of metabolites and the establishment of their detection times. Using PI and NL methods, seven metabolites were observed in post-administration samples. SRM methods allowed for the detection of 13 glucuronide metabolites. The detection times, measured by analysis with an SRM method, were between 1 and 22 days. The metabolite detected for the longest time was 18-nor-17β-hydroxymethyl-17α-methyl-5β-androsta-1,4,13-triene-3-one-17-glucuronide. One metabolite was resistant to hydrolysis with β-glucuronidase; however it was only detected in urine up to four days after administration. The three glucuronide metabolites with the highest retrospectivity were identified by chemical synthesis or mass spectrometric data, and although they were previously reported, this is the first time that analytical data of the intact phase II metabolites are presented for some of them. The LC-MS/MS strategies applied have demonstrated to be useful for detecting glucuronoconjugated metabolites of MTD, including glucuronides resistant to enzymatic hydrolysis which cannot be detected by conventional approaches. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LC‐MS/MS detection of unaltered glucuronoconjugated metabolites of metandienone

Esquivel

Pozo

Garrostas

et al. 2016

Drug Testing and Analysis

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“…Anabolic steroids tend to be extensively metabolised in mammalian species and the development of effective control procedures in sport requires knowledge of the major urinary metabolites to target, for drug screening and confirmatory analysis. The metabolism of methyltestosterone has previously been investigated in detail in man4, 8 and horse3, 9, 10 but to a lesser extent in the greyhound. An early study by Mosbach et al 11.…”

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confidence: 99%

Metabolism of methyltestosterone in the greyhound

Biddle

O’Donnell

Houghton

et al. 2009

Rapid Comm Mass Spectrometry

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Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of methyltestosterone following oral administration to the greyhound. Several metabolites were identified including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17alpha-methyl-5beta-androstane-3alpha-17beta-diol, 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol, and a further compound tentatively identified as 17alpha-methyl-5z-androstane-6z,17beta-triol. The most abundant of these was the 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol. This metabolite was identified by comparison with a reference standard synthesised using a Grignard procedure and characterised using trimethylsilyl (TMS) and acetonide-TMS derivatisation techniques. There did not appear to be any evidence for 16beta-hydroxylation as a phase I metabolic transformation in the greyhound. However, significant quantities of 16alpha-hydroxy metabolites were detected. Selective enzymatic hydrolysis procedures indicated that the major metabolites identified were excreted as glucuronic acid conjugates. Metabolic transformations observed in the greyhound have been compared with those of other mammalian species and are discussed here.

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“…The in vitro observations were finally confirmed by analyzing FIGURE 1 Scheme of methandienone phase I biotransformation pathways reported in literature. [1][2][3][4][5][6][7][8][9][10][11][12][13] M1. 6β,16-dihydroxy-methandienone, M2.…”

mentioning

confidence: 99%

Drug–drug interaction and doping: Effect of non‐prohibited drugs on the urinary excretion profile of methandienone

Mazzarino

Khevenhüller-Metsch

Fiacco

et al. 2018

Drug Testing and Analysis

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The potential consequences of drug-drug interactions on the excretion profile of the anabolic androgenic steroid methandienone (17β-hydroxy-17α-methylandrosta-1,4-dien-3-one) are discussed. More specifically, we have evaluated by in vitro and in vivo experiments the effects of 7 non-prohibited drugs (fluconazole, ketoconazole, itraconazole, miconazole, fluoxetine, paroxetine, and nefazodone) on the main metabolic pathways of methandienone. These are selected among those most commonly used by the athletes. The in vitro assays were based on the use of human liver microsomes, specific recombinant enzyme isoforms of cytochrome P450 and uridine 5'-diphospho-glucuronosyl-transferase. The in vivo study was performed by analyzing urines collected after the oral administration of methandienone with and without the co-administration of ketoconazole. Methandienone and its metabolites were determined by liquid chromatography-mass spectrometry-based techniques after sample pretreatment including an enzymatic hydrolysis step (performed only for the investigation on phase II metabolism) and liquid/liquid extraction with t-butyl methyl-ether. The results from the in vitro experiments showed that the formation of the hydroxylated and dehydrogenated metabolites was significantly reduced in the presence of itraconazole, ketoconazole, miconazole and nefazodone, whereas the production of the 18-nor-hydroxylated metabolites and glucuronidation reactions was reduced significantly only in the presence of ketoconazole and miconazole. The analysis of the post-administration samples confirmed the in vitro observations, validating the hypothesis that drug-drug interaction may cause significant alterations in the metabolic profile of banned drugs, making their detection during doping control tests more challenging.

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In vivo metabolism of Δ, 17α-methyltestosterone in man

Cited by 40 publications

References 7 publications

LC‐MS/MS detection of unaltered glucuronoconjugated metabolites of metandienone

LC‐MS/MS detection of unaltered glucuronoconjugated metabolites of metandienone

Metabolism of methyltestosterone in the greyhound

Drug–drug interaction and doping: Effect of non‐prohibited drugs on the urinary excretion profile of methandienone

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