Studies on anabolic steroids. The mass spectra of 17α-methyl-17β-hydroxy-1,4-androstadien-3-one (dianabol) and its metabolites

Dürbeck, H. W.; Büker, I.

doi:10.1002/bms.1200071007

Cited by 71 publications

(31 citation statements)

References 17 publications

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“…Other major unconjugated metabolites subsequently identi¢ed were the 17a-hydroxy epimer of methandienone (17-epimethandienone) and the 6b-hydroxylated metabolite of epimethandienone. 84,86 In the conjugate fraction of urine, three major bishydroxylated metabolites (5b-H orientation) have been identi¢ed; 88 these steroids have a 3a-hydroxyl group which facilitates conjugation to glucuronic acid in the human. A fourth metabolite has a 1-ene-3-oxo con¢guration but has also been found in the conjugate fraction, 88 presumably because of formation of a 3-hydroxyl group by keto-enol tautomerism, which can then be conjugated with uridine diphosphoglucuronic acid.…”

Section: Metabolism Of Nandrolonementioning

confidence: 99%

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

2003

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International Olympic Committee accredited laboratories play a key role in upholding the principle of fair play and innate ability, as desired by the majority of sports competitors and spectators. Not only does doping damage the image of sport, but it can also be harmful to the individual. The great majority of samples test negative but, when an adverse nding is declared, the analytical data must be of a suf ciently high standard to withstand legal challenges by third parties. The most widely misused performance-enhancing drugs are the anabolic-androgenic steroids, commonly referred to as 'anabolic steroids'. This review attempts to address the complex issues concerning anabolic steroids in sport by considering the clinical, biochemical and analytical perspectives. Fifty years of anabolic steroids and sport: an overviewThe discovery of a process for synthesizing the steroid testosterone (T) from cholesterol in 1935 1 greatly accelerated scienti¢c investigations into the e¡ects of this endogenous androgen. T rapidly became noted for its anabolic properties in increasing muscle size and strength and in its androgenic properties of increasing virilization and aggression. In a comprehensive review of the history of the use of anabolic steroids in sport, Todd 2 noted that, as early as 1945, the science writer Paul de Kreuf had speculated that`it would be interesting to watch the productive power of [a] . . . professional group [of athletes] that would try a systematic supercharge with testosterone . . .'.In the early 1950s, the ¢rst suspicion that T was actually being administered to improve sporting performance came with the allegation that Soviet weightlifters were administering T to gain strength. 2 Also, around that time, pharmaceutical companies were developing synthetic analogues of T with the aim of treating patients in a`catabolic state', the objective being to enhance the anabolic e¡ects of T and to dissociate the unwanted androgenic e¡ects (particularly to minimize the viriliz ing e¡ects). Nandrolone (19-nortestosterone) was the ¢rst synthetic analogue of T to show enough anabolic-androgenic dissociation in animal experiments 3 to justify its introduction as a therapeutic agent. 4 Subsequently, numerous analogues of T [and also its 5a-reduced metabolite, 5a-dihydrotestosterone (DHT)] were developed (see Fig. 1), such as methandienone (methandrostenolone), oxymesterone and stanozolol (for dates of patent awards see Ref. 5). With the growing availability of these licensed compounds, competitors began to experiment with them in an attempt to gain improvements in sporting performance without imparting the full androgenic e¡ects associated with T. During the 1960s, a number of deaths occurred in sports competitors from the use of stimulants and, as a result, in 1967 the International Olympic Committee (IOC) reestablished a medical commission (an IOC Medical Commission was rst established in Athens in 1961; see Ref. 6) which banned the practice of doping in sport, the banned classes including stimula...

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Section: Metabolism Of Nandrolonementioning

confidence: 99%

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

2003

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“…[7][8][9][10][11][12][13] The metabolism of metandienone has been investigated in detail providing the basis for all commonly accepted and employed screening and confirmation procedures for this particular drug in doping controls 8,14-16 using gas chromatography (GC) interfaced to low-or high-resolution mass spectrometry (MS). Major metabolites being used as target analytes in screening assays are 17a-methyl-5a-androstane-3a,17b-diol, 17a-methyl-5b-androstane-3a,17b-diol, 17b-methyl-5b-androst-1-ene-3a,17a-diol (epimetendiol) and 18-nor-17,17-dimethyl-5b-androst-1,13-dien-3a-ol (18-norepimetendiol) (Scheme 1, 3-6), 7,17,18 the latter two of which have allowed long-term detection of metandienone abuse after cessation. Due to the low proton affinity of these compounds, the use of GC/MS after derivatization of target compounds has been preferred over soft ionization techniques such as electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) to identify their presence in doping control specimens.…”

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confidence: 99%

Mass spectrometric identification and characterization of a new long‐term metabolite of metandienone in human urine

Schänzer

Geyer

Fußhöller

et al. 2006

Rapid Comm Mass Spectrometry

119

153

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Anabolic-androgenic steroids are some of the most frequently detected drugs in amateur and professional sports. Doping control laboratories have developed numerous assays enabling the determination of administered drugs and/or their metabolic products that allow retrospectives with respect to pharmacokinetics and excretion profiles of steroids and their metabolites. A new metabolite generated from metandienone has been identified as 18-nor-17beta-hydroxymethyl,17alpha-methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a valuable tool for the long-term detection of metandienone abuse by athletes in sports drug testing. The metabolite was characterized using gas chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem) mass spectrometry by characteristic fragmentation patterns representing the intact 3-keto-1,4-diene structure in combination with typical product ions substantiating the proposed C/D-ring structure of the steroid metabolite. In addition, structure confirmation was obtained by the analysis of excretion study urine specimens obtained after administration of 17-CD(3)-labeled metandienone providing the deuterated analogue to the newly identified metabolite. 18-Nor-17beta-hydroxymethyl,17alpha-methyl-androst-1,4,13-trien-3-one was determined in metandienone administration study urine specimens up to 19 days after application of a single dose of 5 mg, hence providing an extended detection period compared with commonly employed strategies.

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“…1). It has previously been reported that epimerization can lead to different metabolites through an intermediate sulfate conjugate (21,22,24,25,32,33 ). The 17␤-sulfate hydrolyzes in water to several products, including metabolites III and VI.…”

Section: 17-dimethyl-18-norandrosta-1413-trien-3-one (Metabolitementioning

confidence: 99%

“…Three of the 4 detected peaks could be related to compounds previously reported. The most abundant peak (VIIa) can be associated with 17␣-methyl-17␤-hydroxyandrosta-1,4,6-trien-3-one (6-enemethandienone) (22,24,34 ). Two other peaks could be assigned to metabolite VII itself (17 ) and the 17-epimer of VII (VIIc) (27 ), by comparison to authentic reference standards.…”

Section: Trien-3-one (Metabolite Vii)mentioning

confidence: 99%

“…The metabolism of methandienone, a 17␣-methylated anabolic steroid (17)(18)(19), has been thoroughly investigated in the past via administration studies (17, 20 -27 ) and in vitro experiments (2,28 ). The major metabolites reported involve epimerization at the C 17 position and hydroxylation at the 6␤ position (22,23,25 ). Also described in the literature are other metabolic pathways including further reduction of the A-ring (21 ) and hydroxylation at C 16 (24 ).…”

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confidence: 99%

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uPA+/+-SCID Mouse with Humanized Liver as a Model for In Vivo Metabolism of Exogenous Steroids: Methandienone as a Case Study

Lootens¹,

Meuleman

Pozo³

et al. 2009

Clinical Chemistry

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Background: Adequate detection of designer steroids in the urine of athletes is still a challenge in doping control analysis and requires knowledge of steroid metabolism. In this study we investigated whether uPA+/+-SCID mice carrying functional primary human hepatocytes in their liver would provide a suitable alternative small animal model for the investigation of human steroid metabolism in vivo. Methods: A quantitative method based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) was developed and validated for the urinary detection of 7 known methandienone metabolites. Application of this method to urine samples from humanized mice after methandienone administration allowed for comparison with data from in vivo human samples and with reported methandienone data from in vitro hepatocyte cultures. Results: The LC-MS/MS method validation in mouse and human urine indicated good linearity, precision, and recovery. Using this method we quantified 6 of 7 known human methandienone metabolites in the urine of chimeric mice, whereas in control nonchimeric mice we detected only 2 metabolites. These results correlated very well with methandienone metabolism in humans. In addition, we detected 4 isomers of methandienone metabolites in both human and chimeric mouse urine. One of these isomers has never been reported before. Conclusions: The results of this proof-of-concept study indicate that the human liver–uPA+/+-SCID mouse appears to be a suitable small animal model for the investigation of human-type metabolism of anabolic steroids and possibly also for other types of drugs and medications. .

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Studies on anabolic steroids. The mass spectra of 17α-methyl-17β-hydroxy-1,4-androstadien-3-one (dianabol) and its metabolites

Cited by 71 publications

References 17 publications

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

Anabolic steroids in sport: biochemical, clinical and analytical perspectives

Mass spectrometric identification and characterization of a new long‐term metabolite of metandienone in human urine

uPA+/+-SCID Mouse with Humanized Liver as a Model for In Vivo Metabolism of Exogenous Steroids: Methandienone as a Case Study

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