Studies on the Metabolism of C<sub>19</sub> Steroids in Rat Liver

Gustafsson, Jan‐Åke; Lisboa, B. P.; Sjövall, Jan

doi:10.1111/j.1432-1033.1968.tb00389.x

Cited by 44 publications

(3 citation statements)

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“…The ions m/z 147 and 191 seen in the spectra of these compounds are characteristic of the intramolecular rearrangements of trimethylsiloxy groups and their genesis has been discussed in detail by Sloan et al 42. and Gustafsson et al 43. The mechanism for the initial loss of the • CH 2 OSi(CH 3 ) 3 radical, resulting in the formation of the charge‐retained ion at M +.…”

Section: Resultsmentioning

confidence: 96%

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

Dumasia¹

2003

Rapid Comm Mass Spectrometry

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The in vivo phase I biotransformation of 17 alpha-methyltestosterone in the horse leads to the formation of a complex mixture of regio- and stereoisomeric C(20)O(2), C(20)O(3) and C(20)O(4) metabolites, excreted in urine as glucuronide and sulphate phase II conjugates. The major pathways of in vivo metabolism are the reduction of the A-ring (di- and tetrahydro), epimerisation at C-17 and oxidations mainly at C-6 and C-16. Some phase I metabolites have been identified previously by positive ion electron ionisation capillary gas chromatography/mass spectrometry (GC/EI + MS) mainly from the characteristic fragmentation patterns of their methyloxime-trimethylsilyl ether (MO-TMS), enol-TMS or TMS ether derivatives. Following oral administration of 17 alpha-methyltestosterone to two castrated thoroughbred male horses, the glucuronic acid conjugates excreted in post-administration urine samples were selectively hydrolysed by E. coli beta-glucuronidase enzymes. Unconjugated metabolites and the steroid aglycones obtained after enzymatic deconjugation were isolated from urine by solid-phase extraction, derivatised as MO-TMS ethers and analysed by GC/EI + MS. In addition to some of the known metabolites previously identified from the characteristic mass spectral fragmentation patterns of 17 alpha-methyl steroids, some isobaric compounds exhibiting a diagnostic loss of 103 mass units from the molecular ions with subsequent losses of trimethylsilanol or methoxy groups and an absence of the classical D-ring fragment ion were detected. From an interpretation of their mass spectra, these compounds were identified as 17-hydroxymethyl metabolites, formed in vivo in the horse by oxidation of the 17-methyl moiety of 17 alpha-methyltestosterone. This study reports on the GC/EI + MS identification of these novel 17-hydroxymethyl C(20)O(3) and C(20)O(4) metabolites of 17 alpha-methyltestosterone excreted in thoroughbred horse urine.

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Section: Resultsmentioning

confidence: 96%

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

Dumasia¹

2003

Rapid Comm Mass Spectrometry

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“…Some 16(α and β),17β‐dihydroxyandrostanes (e.g., 168 ) produce a major ion, often the base peak, at m/z 191 ( ed ) (Gustafsson et al, ,,; Lisboa, ; Lisboa et al, ) whose mechanism of formation has been discussed by Gustafsson et al () and is outlined in Scheme .…”

Section: Trimethylsilyl Derivativesmentioning

confidence: 99%

“…(Adapted from Gustafsson et al. ()) and (c) 3α,16α,20α‐trihydroxy‐5α‐pregnane ( 171 ). (Adapted from Gustafsson ()).…”

Section: Trimethylsilyl Derivativesmentioning

confidence: 99%

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Harvey

Vouros

2019

Mass Spectrometry Reviews

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This review describes the mass spectral fragmentation of trimethylsilyl (TMS) and related alkylsilyl derivatives used for preparing samples for analysis, mainly by combined gas chromatography and mass spectrometry (GC/MS). The review is divided into three sections. The first section is concerned with the TMS derivatives themselves and describes fragmentation of derivatized alcohols, thiols, amines, ketones, carboxylic acids and bifunctional compounds such as hydroxy‐ and amino‐acids, halo acids and hydroxy ethers. More complex compounds such as glycerides, sphingolipids, carbohydrates, organic phosphates, phosphonates, steroids, vitamin D, cannabinoids, and prostaglandins are discussed next. The second section describes intermolecular reactions of siliconium ions such as the TMS cation and the third section discusses other alkylsilyl derivatives. Among these latter compounds are di‐ and trialkyl‐silyl derivatives, various substituted‐alkyldimethylsilyl derivatives such as the tert‐butyldimethylsilyl ethers, cyclic silyl derivatives, alkoxysilyl derivatives, and 3‐pyridylmethyldimethylsilyl esters used for double bond location in fatty acid spectra. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 0000:1–107, 2019

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Mass spectra of trimethylsilyl ethers of some Δ⁵‐3β‐hydroxy C ₁₉ steroids

Brooks

Harvey

Middleditch

et al. 1973

Org. Mass Spectrom.

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Abstract-The mass spectra (20 eV electron energy) of a wide range of A5-3B-hydroxy C,, steroid TMS ethers have been examined with the aid of high-resolution mass measurements, together with deuterium and oxygen-18 labelling data. The validity of many previously proposed fragmentation modes has been confirmed. A number of ions regarded as diagnostic have been shown to be less specific than had been formerly supposed. Several novel fragmentations have been observed and investigated. I N T R O D U C T I O NCHOLESTEROL is present in practically all living organisms, and is the primary source of mammalian steroidal hormones. It may, for example, be metabolised to progesterone via 20,22-dihydroxycholesterol and pregnenolone. Alternatively, complete oxidative removal of the side chain leads to dehydroepiandrosterone (I) and to the C,, hormonal steroids. The A5-3j3-hydroxy steroids are precursors of hormones with the A4-3-one structure.l Consequently, A5-3p-hydroxy C,,-steroids (or their conjugates) are found in quantity only if 3,%hydroxysteroid dehydrogenase is not actively converting them to A4-3-keto steroids. This situation is encountered, for example, in newborn mammals and in certain pathological conditions.2The technique of combined gas chromatography-mass spectrometry (g.c.-m.s.) has been used in the identification of a large number of A5-3j3-hydroxy C,,-steroids, as their trimethylsilyl (TMS) ether derivatives. The following are representative of many samples studied: urine3 to and f a e c e~~~~.~ of newborn and infant humans, meconium of newborn humans,7 human umbilical cord p l a~m a ,~ human amniotic fluid,1° human bile,,, human peripheral plasma,12 to l5 plasma and urine of an eightyear old boy with 3p-hydroxy steroid dehydrogenase deficiency,16 urine of a pregnant irus monkey17 and of a newborn chimpanzee,18 and urine and faeces of female germfree and 'conventional' rats treated with a 3~-hydroxy-A5-oxidoreductase inhibitor.lg G.c.-m.s. has also been used to show that A5-3/3-hydroxy steroids were not excreted by an anencephalic newborn infant.20Despite the clinical significance of androstenols,21 there has been no systematic survey of the mass spectral fragmentations of their derived TMS ethers. We have accordingly examined the low-resolution mass spectra of a number of these compounds, and with the aid of isotope-labelling experiments and high-resolution mass measurements, have elucidated some routes of fragmentation. 925

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Studies on the Metabolism of C₁₉ Steroids in Rat Liver

Cited by 44 publications

References 20 publications

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Mass spectra of trimethylsilyl ethers of some Δ⁵‐3β‐hydroxy C ₁₉ steroids

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Studies on the Metabolism of C19 Steroids in Rat Liver

Cited by 44 publications

References 20 publications

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Mass spectra of trimethylsilyl ethers of some Δ5‐3β‐hydroxy C 19 steroids

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Studies on the Metabolism of C₁₉ Steroids in Rat Liver

Mass spectra of trimethylsilyl ethers of some Δ⁵‐3β‐hydroxy C ₁₉ steroids