Matrix-enhanced time-of-flight secondary ion mass spectrometry for the detection of drugs in biological tissues : Improving the detection of diclofenac and moxifloxacin in the cornea

Details

Supervisors

Delcorte, Arnaud ; Dupont-Gillain, Christine C.

Faculty

Faculté des bioingénieurs

Degree label

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

Abstract

enIn pharmacology, it is crucial to assess the chemical action of a drug but also its tissue distribution inside an organ. Several techniques have been used throughout the years to achieve this goal, but they might suffer from negative aspects concerning drug detection. Recently, Secondary Ion Mass Spectrometry (SIMS) has shown promising results in the biomedical field because of its ability to detect and (co)-localize biomolecules and organic compounds at the tissue surface without a labelling process that could alter the analyte distribution. Nevertheless, the intrinsic chemical complexity of tissue sections can interfere with and compromise analyte detection via SIMS analysis. Moreover, organic molecules, especially pharmaceutical compounds, display low ionization probabilities, which significantly limit detection sensitivity. This study explores the transfer of an ocular drug onto the surface of a sublimated matrix in order to enhance its detection by SIMS and ultimately inside the cornea (tissue). The drugs examined were diclofenac and moxifloxacin. Each drug was deposited onto three different MALDI-type (Matrix Assisted Laser Desorption Ionization) matrices to determine which one provided the greatest improvement in detection: α-cyano-4-hydroxycinnamic acid (CHCA), 2-mercaptobenzothiazole (MBT), and 2,4,6-trihydroxyacetophenone (THAP). This process was performed inside the ToF-SIMS analysis chamber where the gas cluster ion beam (GCIB) is used to sputter-transfer the drug from a target to the matrix collector. THAP produced the greatest enhancement of the diclofenac signal, whereas both CHCA and THAP enhanced the moxifloxacin signal with SIMS analysis. The tissue analysis (with the drug spotted on it) yielded similar results, demonstrating enhanced drug detection with the appropriate matrices. Furthermore, CHCA and THAP increased the intensity of the cornea-related signal, corresponding to phosphocholine species originating from the membranes of corneal epithelial cells.