Novel perfluoroacyl derivatives of corticosteroids and related substances for potential use in quantitative gas chromatography mass spectrometry

Abstract

We investigated the potential of perfluoroacylation for gas chromatographic mass spectrometric determination of corticosteroids and related substances. Structure elucidation of the reaction products was performed with high and low resolution mass spectrometry and with proton and carbon nuclear magnetic resonance spectrometry. Besides the well known 3-enol ester formation, 17β-methyl-18-nor-13(14)-ene steroids were formed via loss of the 17-α hydroxyl group followed by a Wagner-Meerwein rearrangement. Compounds that bear an 11β-hydroxy group formed additionally a 9(11) double bond when acetone was used as solvent, whereas acetonitrile or cyclohexane led to formation of 11β-perfluoroacyl esters. In particular, perfluoroacylation of cortisol led to a clearly defined product instead of complex mixtures observed before, which thus makes it a valuable alternative to methoxime formation-silylation of cortisol for quantitative gas chromatographic mass spectrometric analyses.

Ultra-Sensitive Quantification of Corticosteroids in Plasma Samples Using Selective Solid-Phase Extraction and Reversed-Phase Capillary High-Performance Liquid Chromatography/Tandem Mass Spectrometry

“…A wide range of methodologies has been developed for the determination of corticosteroids in complex matrices. Traditional analytical approaches include radioimmunoassay (RIA), − gas chromatography/mass spectrometry (GC/ MS), , and high performance liquid chromatography (HPLC) coupled to UV, , fluorescence, , or RIA detection . Recently liquid chromatography coupled to electrospray/atmospheric pressure chemical ionization (ESI/APCI) mass spectrometry (LC/MS) has been applied to the quantification of corticosteroids in biological fluids. ,− This technique provides good sensitivity and selectivity and eliminates laborious sample preparation procedures that are necessary for methodologies like RIA, GC/MS, and HPLC fluorescence.…”

Bismuth(III) triflate-catalyzed rearrangement of 16α,17α-epoxy-20-oxosteroids. Synthesis and structural elucidation of new 16α-substituted 17α-alkyl-17β-methyl-Δ13-18-norsteroids

“…The molecular structures of compounds 9 and 14 are shown in Figures 3 and 4, as an ORTEP diagram with the corresponding atom numbering scheme. In both molecules, the five-membered D-ring has a C15-envelope conformation as shown by the Cremer and Pople parameters 61 [9: q 2 ¼0.180(7) Å, 4 2 ¼108(2) 14: 0.174(3) Å, 4 2 ¼112.9(9) ] and asymmetry parameters 62 [9: DC s (16)¼DC s (13,14)¼0.2(6) ;; 14: DC s (16)¼DC s (13,14)¼1.9(3) ;]. The typical 18-CH 3 group is absent on their structure and a C13]C14 double bond is present at rings C and D fusion, with a bond length of 1.318(7) Å and 1.327(3) Å, for compounds 9 and 14, respectively.…”

“…7-12 A similar rearrangement has been described by Stö ckl et al during the study of perfluoracylation for gas chromatographic mass spectrometric determination of anabolic steroids bearing a tertiary C17-hydroxy group, corticosteroids and related compounds. [13][14][15] Schneider et al reported that a steroid bearing the 16a,17a-fused oxetan group was converted into a 16a-hydroxymethyl-17b-methyl-D 13 -18-nor derivative. 16 The formation of 17a,17b-dimethyl-D 13 -18-norsteroids from 17b-sulfate derivatives of anabolic 17a-methylsteroids has also been described.…”