Ratiometric analysis of the ferrocene boronate esters of 2- and 4-hydroxyestradiol by tandem electrospray mass spectrometry

Abstract

A method has been developed for the semiquantitative analysis of the catechol estrogens, 2‐ and 4‐hydroxyestradiol, using tandem electrospray mass spectrometry in a quadrupole ion trap mass analyzer. The implication of catechol estrogens in the biogenesis of breast and prostate cancer makes these labile lipophilic compounds important analytical targets. Ferrocene boronic acid is reacted with 2‐ and 4‐hydroxyestradiol to form their cyclic boronate esters. Sample ionization is accomplished during the electrospray process by a one‐electron oxidation of the ferrocene functionality to form the radical cation. The analysis depends on a non‐aqueous solvent system consisting of 90% acetonitrile and 10% dichloromethane with 100 µM lithium triflate as the supporting electrolyte. The sensitivity of the analysis is greatly increased by the use of a novel electrospray interface with a large surface area stainless steel electrode coupled to a pulled fused‐silica needle. Collision‐induced dissociation of the selected molecular ion within the ion trap produces fragment ion spectra that can be used to distinguish between the two isobaric isomers and ultimately determine the relative amounts in mixtures containing both components. The method is sensitive to analyte concentrations in the low nM range. Copyright © 2001 John Wiley & Sons, Ltd.

On-line electrochemistry – MS and related techniques

“…Distinction between the diastereomers of mono-and disaccharides was achieved. The same arrangement was used for semiquantitative analysis of the derivatized catechol estrogens, 2-and 4-hydroxyestradiol [62]. Collision-induced dissociation of the radical cations produced fragment ion spectra that enabled distinction between the two isobaric isomers.…”

Analysis of cysteine-containing proteins using precolumn derivatization with N-(2-ferroceneethyl)maleimide and liquid chromatography/electrochemistry/mass spectrometry

“…1 (20 mL) and mixed with 220 mg (2.4 mmol) maleic anhydride, which was also dissolved in dry THF (10 mL). After stirring the reaction mixture for one hour in an ice bath, the solvent was removed by evaporation and the crude N-(2-ferroceneethyl)maleic acid (4) obtained was, in contrast to the approach described in the literature [12], purified by column liquid chromatography using silica gel with ethyl acetate/chloroform (9:1) as the mobile phase. ESI-MS: m/z = 327 [M+H] + .…”

“…Ferrocene-based derivatizing agents were used for other classes of compounds too. Semiquantitative analysis of catechol estrogens as their ferrocene boronate esters using ESI-MS with one-electron oxidation in the source using a nonaqueous solvent system (a mixture of dichloromethane and acetonitrile (ACN) with lithium triflate as the working electrolyte) was applied by Williams et al [12]. 1α-Hydroxyvitamin D 3 in rat plasma was determined by ESI-MS after derivatization with 4-ferrocenylmethyl-1,2,4-triazoline-3,5-dione by Murao et al [13].…”

Electron-capturing Derivatization of Neutral Steroids for Increasing Sensitivity in Liquid Chromatography/Negative Atmospheric Pressure Chemical Ionization-Mass Spectrometry

“…Due to susceptibility of the boronates to solvolysis, they have generally been used in normal-phase LC. 10 However, Gamoh and co-workers have demonstrated the utility of boronates for characterization of 1,2-diol compounds in reversed-phase LC 11 and LC/MS. 12 We also found that the boronates examined in this study were remarkably stable in the mobile phase using MeCN, though they were solvolyzed in aqueous MeOH.…”