Matrix-enhanced secondary ion mass spectrometry of hydrophilic pharmaceutical compounds, Improving the detection of gemcitabine anti-cancer drug in biological tissue samples

Details

Supervisors

Dupont-Gillain, Christine C. ; Delcorte, Arnaud

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

Secondary ion mass spectrometry (SIMS) is an analytical method that shows great potential in biomedical sciences and pharmacology since it enables to simultaneously detect and (co)localise organic compounds and biomolecules at the surface of tissue sections without the need for a labelling process that could impact the distribution of the analytes. It uses a beam of primary ions to probe the sample surface and generate secondary ions that will then enter a mass analyser. It is also possible to erode the sample using a beam of large cluster ions, thus enabling to perform depth profiles and 3D analyses. For example, in studies investigating the local delivery of pharmaceutical compounds to an organ from a gel or another biomaterial, SIMS analyses can deliver game-changing information about the distribution of the drug compound(s) inside the different structures. However, SIMS faces sensitivity issues when it comes to the analysis of organic compounds in biological samples. Indeed, tissue sections are complex matrices in which the chemical environment can negatively impact the detection of the analytes. Additionally, the ionisation probability and therefore the sensitivity is very low for certain classes of organic molecules. Among others, it is the case for hydrophilic pharmaceutical compounds. This work investigates the possibility to transfer a layer of matrix compound to the surface of a mouse brain section spotted with gemcitabine, a hydrophilic chemotherapeutical drug, to improve the detection of the pharmaceutical compound in SIMS. This process takes place inside the chamber of a ToF-SIMS apparatus where the gas cluster ion beam (GCIB) is used to sputter-transfer the matrix from a reservoir to the sample. The matrix compounds used in this study are low-molecular weight organic acids used in MALDI-MS (matrix-assisted laser desorption/ionisation mass spectrometry). The in situ transfer of α-cyano-4-hydroxycinnamic acid (CHCA) successfully enhanced the signal of the intact molecular ion of gemcitabine as well as the signal of phosphatidylcholines, a category of phospholipids that received a lot of interest from the SIMS community. The potential of citric acid, an organic acid that cannot be used as a matrix in MALDI, was also investigated for the matrix-enhanced SIMS (ME-SIMS) of hydrophilic pharmaceutical compounds. It was added to an aqueous solution of gemcitabine hydrochloride and the mixture was drop-deposited on silicon wafers before being analysed. Taking into account the dilution effect happening when an important amount of matrix is added to the analyte, the results indicated that citric acid had a positive influence on the detection of the intact molecular ion of gemcitabine.