Thin layer chromatography-matrix assisted laser desorption ionisation-mass spectrometry of pharmaceutical compounds.
type: CreativeWork
description: Thin-layer chromatography (TLC) is of great importance for the pharmaceutical industry as a simple, quick, and low cost analytical method. Considerable effort has been made over the past decades to combine the simplicity of TLC with the selectivity and sensitivity of mass spectrometry (MS) detection. In the pharmaceutical industry sensitivity is an especially important factor, since the allowed impurity level of most drugs is under 0.1%.The aim of the present thesis was to develop methods for the direct examination of pharmaceutical compounds from TLC plates by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI TOF MS). The study was started by comparing several approaches for the application of the matrix for direct TLC-MALDI including a newly developed electrospray matrix deposition method. This new method was found to be superior to the other techniques studied. It produced a stable signal, minimised analyte spreading, and hence allowed the scanning of a TLC plate to obtain chromatographic as well as mass spectral data. The plotted mass chromatograms assisted in spot location, and allowed the calculation of Rf-values. These showed good agreement with the Rf -values determined by UV detection. The decrease in mass resolution and mass accuracy commonly observed in TLC-MALDI TOF MS due to the uneven nature of the silica gel layer was corrected by internal recalibration on selected matrix ions during the scanning of the TLC plate. To enhance the signals recorded directly from a TLC plate the use of an extraction solvent prior the matrix application was explored. Further improvements in sensitivity were obtained by modifying a robotic x-y-z axis motion system to act as an electrospray deposition device and by use of special Si 60 F[254] HPTLC-MALDI targets. Using both approaches sensitivities in the high fmol range were obtained. To minimise matrix interference, which can suppress analyte signals, the application of suspensions of part…
abstract: Thin-layer chromatography (TLC) is of great importance for the pharmaceutical industry as a simple, quick, and low cost analytical method. Considerable effort has been made over the past decades to combine the simplicity of TLC with the selectivity and sensitivity of mass spectrometry (MS) detection. In the pharmaceutical industry sensitivity is an especially important factor, since the allowed impurity level of most drugs is under 0.1%.The aim of the present thesis was to develop methods for the direct examination of pharmaceutical compounds from TLC plates by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI TOF MS). The study was started by comparing several approaches for the application of the matrix for direct TLC-MALDI including a newly developed electrospray matrix deposition method. This new method was found to be superior to the other techniques studied. It produced a stable signal, minimised analyte spreading, and hence allowed the scanning of a TLC plate to obtain chromatographic as well as mass spectral data. The plotted mass chromatograms assisted in spot location, and allowed the calculation of Rf-values. These showed good agreement with the Rf -values determined by UV detection. The decrease in mass resolution and mass accuracy commonly observed in TLC-MALDI TOF MS due to the uneven nature of the silica gel layer was corrected by internal recalibration on selected matrix ions during the scanning of the TLC plate. To enhance the signals recorded directly from a TLC plate the use of an extraction solvent prior the matrix application was explored. Further improvements in sensitivity were obtained by modifying a robotic x-y-z axis motion system to act as an electrospray deposition device and by use of special Si 60 F[254] HPTLC-MALDI targets. Using both approaches sensitivities in the high fmol range were obtained. To minimise matrix interference, which can suppress analyte signals, the application of suspensions of part…
author: Crecelius, Anna Christina.
language: en
date published: 2002
date modified: 2026-07-24T06:31:18Z
provider: Sheffield Hallam University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Sheffield Hallam University (United Kingdom).