171199-96-5Relevant academic research and scientific papers
Gas chromatography/chemical ionization triple quadrupole mass spectrometry analysis of anabolic steroids: Ionization and collision-induced dissociation behavior
Polet, Michael,Van Gansbeke, Wim,Van Eenoo, Peter,Deventer, Koen
, p. 511 - 522 (2016/02/09)
Rationale The detection of new anabolic steroid metabolites and new designer steroids is a challenging task in doping analysis. Switching from electron ionization gas chromatography triple quadrupole mass spectrometry (GC/EI-MS/MS) to chemical ionization (CI) has proven to be an efficient way to increase the sensitivity of GC/MS/MS analyses and facilitate the detection of anabolic steroids. CI also extends the possibilities of GC/MS/MS analyses as the molecular ion is retained in its protonated form due to the softer ionization. In EI it can be difficult to find previously unknown but expected metabolites due to the low abundance or absence of the molecular ion and the extensive (and to a large extent unpredictable) fragmentation. The main aim of this work was to study the CI and collision-induced dissociation (CID) behavior of a large number of anabolic androgenic steroids (AAS) as their trimethylsilyl derivatives in order to determine correlations between structures and CID fragmentation. Clarification of these correlations is needed for the elucidation of structures of unknown steroids and new metabolites. Methods The ionization and CID behavior of 65 AAS have been studied using GC/CI-MS/MS with ammonia as the reagent gas. Glucuronidated AAS reference standards were first hydrolyzed to obtain their free forms. Afterwards, all the standards were derivatized to their trimethylsilyl forms. Full scan and product ion scan analyses were used to examine the ionization and CID behavior. Results Full scan and product ion scan analyses revealed clear correlations between AAS structure and the obtained mass spectra. These correlations were confirmed by analysis of multiple hydroxylated, methylated, chlorinated and deuterated analogs. Conclusions AAS have been divided into three groups according to their ionization behavior and into seven groups according to their CID behavior. Correlations between fragmentation and structure were revealed and fragmentation pathways were postulated.
Syntheses of stable isotope-labeled 6β-hydroxycortisol, 6β-hydroxycortisone, and 6β-hydroxytestosterone
Furuta, Takashi,Suzuki, Atsushi,Matsuzawa, Mitsuhiro,Shibasaki, Hiromi,Kasuya, Yasuji
, p. 693 - 703 (2007/10/03)
A method is described for the preparation of two types of multi-labeled 6β-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H5]cortisone and [1,2,4,19- 13C4,1,1,19,19,19-2H5]cortisone (cortisone-2H5-BMD and cortisone-13C 4,2H5-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H5]- or [1,3- 13C2,1,1,3,3,3-2H5]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H6]- or [1,3-13C 2,1,1,1,3,3,3-2H6]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6β-hydroxy-[1,1,19,19,19- 2H5]cortisone-BMD and 6β-hydroxy-[1,2,4,19- 13C4,1,1,19,19,19-2H5]cortisone-BMD, respectively, as a mixture of 6β- and 6α-epimers in a ratio of 4:1. Separation of 6β- and 6α-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6β-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6β-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH4 and subsequent removal of the C-3 and C-17 protecting groups gave 6β-hydroxy-[1,1,19,19,19-2H5]cortisol (6β-hydroxycortisol-2H5) and 6β -hydroxy-[1,2,4,19-13C4,1,1,19,19,19-2H 5]cortisol (6β-hydroxycortisol-13C4, 2H5), respectively, as a mixture of 6β- and 6α-epimers (6β:6α=4.4:1). The isotopic compositions of 6β-hydroxycortisol-2H5 and 6β -hydroxycortisol-13C4,2H5 were 90.9 and 92.1 at.%, respectively. Furthermore, 6β-hydroxy-[1α ,16,16,17α-2H4]testosterone was synthesized by the UV irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivative of deuterium-labeled testosterone ([1α,16,16,17α- 2H4]testosterone) obtained by using catalytic deuteration and hydrogen-deuterium exchange reactions.
One-pot deuteration and reduction of ketones in the synthesis of [16,16,17-2H3]-epitestosterone
Chodounska, Hana,Kasal, Alexander,Saman, David,Ubik, Karel
, p. 1037 - 1046 (2007/10/03)
5α-Androstan-17-one and 6β-methoxy-3α,5-cyclo-5α-androstan-17-one were reduced by sodium in deuterium oxide to [16,16,17-2H3]-17β-alcohols. The 17β-tosyloxy group of [16,16,17-2H 3]-6β-methoxy-3α,5-cyclo-5α-andr
The Selective Protection of the 3-Ketone Functions of Steroids as Heptafluoro-p-tolyl Enol Ethers
Jarman, Michael,McCague, Raymond
, p. 1129 - 1134 (2007/10/02)
Conjugated and unconjugated 3-ketone functions in steroids react with octafluorotoluene at above 100 deg C in the presence of caesium fluoride to give heptafluoro-p-tolyl enol ethers.The related but unusually reactive Wieland-Miescher ketone (11) reacted at room temperature in the presence of tetra-n-butylammonium fluoride.Enones were regenerated from their derivatives by acidic hydrolysis.Hydrolysis of the derivative (10) of 4,5α-dihydroxytestosterone was slu but sodium methoxide regenerated the parent steroid.The methods have been applied in a synthesis of deuterium-labelled testosterone.
Heptafluoro-p-tolyl as a Selective Protecting Group for the Enone Function of Androst-4-ene-3,17-dione: Application to the Preparation of Deuterium-labelled Testosterone
Jarman, Michael,McCague, Raymond
, p. 635 - 636 (2007/10/02)
Octafluorotoluene reacts with the enone function of androst-4-ene-3,17-dione in the presence of caesium fluoride to give specifically a 3,5-dienol ether which has been used to prepare deuterium-labelled testosterone.
