Mass spectrometry in structural and stereochemical problems. 254. Elucidation of the course of the electron impact induced fragmentation of .alpha.,.beta.-unsaturated 3-keto steroids

Brown, Frederick J.; Djerassi, Carl

doi:10.1021/ja00522a061

Cited by 57 publications

(20 citation statements)

References 12 publications

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“…The preparation of enol-TMS ethers of steroids with a 3-keto-androst-1-ene or 3-ketoandrost-4-ene generating 3-hydroxy-1,3-diene or 3-hydroxy-2, 4-diene derivatives gives rise to mass spectra containing an abundant fragment at m/z 194 (Table 2, 3 and 5) as shown for testosterone in Figure 1c (Schänzer, Geyer, & Donike, 1991;. Deuterium exchange experiments substantiated a proposed fragmentation route including the fissions of the bonds between C-6 and C-7 as well as C-9 and C-10 according to dissociation pathways of comparable underivatized steroids as described by Djerassi and co-workers (Shapiro & Djerassi, 1964b;Brown & Djerassi, 1980). Steroidal structures comprising a 1,4-dien-3-one are also enolized by means of trimethylsilylation and generate an intense fragment ion at m/z 206 as observed for instance with 1-dehydrotestosterone (Table 2, 6) or metandienone (Schänzer, Geyer, & Donike, 1991;Schänzer, Opfermann, & Donike, 1992;.…”

Section: Ms In Sports Drug Testingsupporting

confidence: 57%

Mass spectrometry in sports drug testing: Structure characterization and analytical assays

Thevis

Schänzer

2006

Mass Spectrometry Reviews

177

128

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Owing to the sensitive, selective, and unambiguous nature of mass spectrometric analyses, chromatographic techniques interfaced to various kinds of mass spectrometers have become the most frequently employed strategy in the fight against doping. To obtain utmost confidence in analytical assays, mass spectrometric characterization of target analytes and typical dissociation pathways have been utilized as basis for the development of reliable and robust screening as well as confirmation procedures. Methods for qualitative and/or quantitative determinations of prohibited low and high molecular weight drugs have been established in doping control laboratories preferably employing gas or liquid chromatography combined with electron, chemical, or atmospheric pressure ionization followed by analyses using quadrupole, ion trap, linear ion trap, or hyphenated techniques. The versatility of modern mass spectrometers enable specific as well as comprehensive measurements allowing sports drug testing laboratories to determine the misuse of therapeutics such as anabolic-androgenic steroids, stimulants, masking agents or so-called designer drugs in athletes' blood or urine specimens, and a selection of recent developments is summarized in this review.

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Section: Ms In Sports Drug Testingsupporting

confidence: 57%

Mass spectrometry in sports drug testing: Structure characterization and analytical assays

Thevis

Schänzer

2006

Mass Spectrometry Reviews

177

128

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“…Epimerization at C(17) of the c 1 8 and C,, anabolic steroids and their primary metabolites prior to conjugation with glucuronic acid has been previously reported in horses. l-' In man the epimerization of the tertiary alcohol at C (17) in Dianabol has also been rep~rted.'~. '~ Although metabolite 1, a minor metabolite, was identified in fraction G1 after hydrolysis, it is assumed to be excreted in the urine as unconjugated steroid and not as an enol glucuronide.…”

Section: Discussionmentioning

confidence: 99%

Biotransformation of 1-dehydrotestosterone in the equine male castrate: Identification of the neutral unconjugated and glucuronic acid conjugated metabolites in horse urine

Dumasia¹,

Houghton²

1988

Biol. Mass Spectrom.

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The in vivo biotransformation of (1,2(n)-3H)1-dehydrotestosterone was studied in three equine male castrates and a number of neutral metabolites were identified in the urinary unconjugated and glucuronic acid conjugate fractions by gas chromatography/mass spectrometry. The metabolites were extracted from aliquots of the 0-24 h urine samples by Amberlite XAD-2 and separated into combined unconjugated plus glucuronic acid conjugated and sulphoconjugated fractions by Sephadex LH-20 column chromatography. After enzymatic hydrolysis of the glucuronides, the crude neutral unconjugated steroids plus the aglycones were partially purified by Kieselgel H chromatography and identified as their methyloxime trimethylsilyl derivatives. In the unconjugated fraction, the major metabolites were isomers of androsta-1,4-diene-6,16,17-triol-3-one. In the aglycone fraction a small amount of the parent steroid was present but the major metabolite was the 17 alpha isomer androsta-1,4-dien-17 alpha-ol-3-one. Other metabolites containing the 1,4-dien-3-one group were isomers of androsta-1,4-diene-16,17-diol-3-one and androsta-1,4-diene-6,16-diol-3-one. Reduction of the 4-ene functionality leading to the formation of 5-androst-1-en-16-ol-3,17-dione, 5-androst-1-ene-16,17-diol-3-one and of the 1-ene functionality leading to the formation of testosterone and its further reduction leading to the formation of C19O2 and C19O3 androstane metabolites was observed. Some interesting features on the electron impact fragmentations of the methyloxime trimethylsilyl derivatives of steroids containing a 1,4-dien-3-one group were also observed.

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“…While interpretation of mass spectra obtained under electron ionization (EI) conditions is well understood and documented [13,14], interpretation of product-ion spectra of [M ϩ H] ϩ ions acquired under atmospheric pressure ionization (API) MS/MS conditions is generating new interest. Fragmentation pathways are reported for testosterone and testosterone hydroxyl analogs [15], oxosteroid Girard derivatives [16,17], and steroid oximes [18] under ESI conditions.…”

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confidence: 99%

Collision-induced dissociation pathways of anabolic steroids by electrospray ionization tandem mass spectrometry

Guan

Soma

Luo

et al. 2006

J. Am. Soc. Mass Spectrom.

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Anabolic steroids are structurally similar compounds, and their product-ion spectra obtained by tandem mass spectrometry under electrospray ionization conditions are quite difficult to interpret because of poly-ring structures and lack of a charge-retaining center in their chemical structures.In the present study, the fragmentation of nine anabolic steroids of interest to the racing industry was investigated by using triple quadrupole mass spectrometer, Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and a linear ion trap instrument. With the aid of an expert system software (Mass Frontier version 3.0), accurate mass measurements, and multiple stage tandem mass spectrometric (MS n ) experiments, fragmentation pathways were elucidated for boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, normethandrolone and mibolerone. Small differences in the chemical structures of the steroids, such as an additional double-bond or a methyl group, result in significantly different fragmentation pathways. The fragmentation pathways proposed in this paper allow interpretation of major product ions of other anabolic steroids reported by other researchers in a recent publication [19]. The proposed fragmentation pathways are helpful for characterization of new steroids. The approach used in this study for elucidation of the fragmentation pathways is helpful in interpretation of complicated product-ion spectra of other compounds, drugs and their metabolites. (J Am Soc Mass Spectrom 2006, 17, 477-489)

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Mass spectrometry in structural and stereochemical problems. 254. Elucidation of the course of the electron impact induced fragmentation of .alpha.,.beta.-unsaturated 3-keto steroids

Cited by 57 publications

References 12 publications

Mass spectrometry in sports drug testing: Structure characterization and analytical assays

Mass spectrometry in sports drug testing: Structure characterization and analytical assays

Biotransformation of 1-dehydrotestosterone in the equine male castrate: Identification of the neutral unconjugated and glucuronic acid conjugated metabolites in horse urine

Collision-induced dissociation pathways of anabolic steroids by electrospray ionization tandem mass spectrometry

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