Detection and imaging of pharmaceutical compounds in skin by MALDI-MS.
type: CreativeWork
description: Mass spectrometric techniques have been developed recently for the examination of biological tissue samples. Tandem mass spectrometry has been employed for the detection of pharmaceutical compounds and also mass spectrometric 'images' have been produced which show the spatial distribution of peptides, proteins and drugs in tissue.In this thesis, a programme of method development for the detection and imaging of topically applied pharmaceutical compounds in porcine epidermal tissue by MALDI-TOF-MS is presented. Direct analysis of fresh tissue sections was compared with the analysis of tissue imprints formed by blotting onto a variety of substrates. The samples were coated with matrix material by a prototype electrospray deposition device. Analyses were performed on a linear time-of-flight (LaserTOF 1500, SAI) mass spectrometer. Direct analysis of tissue and analysis of the C18 blots gave irreproducible data. Problems with matrix layer in-homogeneity were experienced with nitrocellulose and polyvinyl difluoride (PVDF) membranes. Reproducible data were obtained by analysis of tissue imprints created on carbon and cellulose membranes. All subsequent work was conducted using an Applied Biosystem Qstar pulsar i hybrid quadrupole time-of-flight mass spectrometer fitted with an orthogonal MALDI ion source and ion imaging software. The advantages of superior mass accuracy and resolution with such an instrument configuration were investigated.Electrospray and airspray methods were compared for analysis of tissue imprinted carbon and cellulose membranes. A novel method of pre-coating cellulose membranes in matrix by airspray prior to the blotting procedure was developed. The method was found to retain the expected distribution of the analyte.Ion images demonstrating the permeation of the applied compound into the skin were achieved by imaging a cross sectional imprint of treated tissue on a cellulose membrane precoated in matrix material. A calibration graph for the determinat…
abstract: Mass spectrometric techniques have been developed recently for the examination of biological tissue samples. Tandem mass spectrometry has been employed for the detection of pharmaceutical compounds and also mass spectrometric 'images' have been produced which show the spatial distribution of peptides, proteins and drugs in tissue.In this thesis, a programme of method development for the detection and imaging of topically applied pharmaceutical compounds in porcine epidermal tissue by MALDI-TOF-MS is presented. Direct analysis of fresh tissue sections was compared with the analysis of tissue imprints formed by blotting onto a variety of substrates. The samples were coated with matrix material by a prototype electrospray deposition device. Analyses were performed on a linear time-of-flight (LaserTOF 1500, SAI) mass spectrometer. Direct analysis of tissue and analysis of the C18 blots gave irreproducible data. Problems with matrix layer in-homogeneity were experienced with nitrocellulose and polyvinyl difluoride (PVDF) membranes. Reproducible data were obtained by analysis of tissue imprints created on carbon and cellulose membranes. All subsequent work was conducted using an Applied Biosystem Qstar pulsar i hybrid quadrupole time-of-flight mass spectrometer fitted with an orthogonal MALDI ion source and ion imaging software. The advantages of superior mass accuracy and resolution with such an instrument configuration were investigated.Electrospray and airspray methods were compared for analysis of tissue imprinted carbon and cellulose membranes. A novel method of pre-coating cellulose membranes in matrix by airspray prior to the blotting procedure was developed. The method was found to retain the expected distribution of the analyte.Ion images demonstrating the permeation of the applied compound into the skin were achieved by imaging a cross sectional imprint of treated tissue on a cellulose membrane precoated in matrix material. A calibration graph for the determinat…
author: Bunch, Josephine.
language: en
date published: 2005
date modified: 2026-07-24T06:31:14Z
provider: Sheffield Hallam University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Sheffield Hallam University (United Kingdom).