Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging

Sophie Strindberg, Jakob Plum, Charlotte Bagger, Christian Janfelt*, Anette Müllertz*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

1 Citation (Scopus)

Abstract

Mapping the spatial distribution of a drug throughout the gastrointestinal tract (GIT) after oral ingestion can provide novel insights into the interaction between the drug, the oral drug delivery system, and the GIT. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a molecular imaging technique that can analyze molecules in the cryosections of tissues, determining their localization with a spatial resolution of 10-100 μm. The overall aim of this study was to use MALDI-MSI to visualize the distribution and spatial location of a model prodrug (fenofibrate) through the rat GIT. Furthermore, the distribution and spatial colocalization of taurocholate and phospholipids in the rat GIT in relation to fenofibrate were investigated. Rats were given a fenofibrate suspension of 10 mg/mL by oral gavage. Blood samples were drawn, and the rats were euthanized at three different time points. The GIT was collected and frozen, and MALDI-MSI was applied on cross sections of the stomach and intestine. Fenofibrate was detected by MALDI-MSI throughout the GIT, which also revealed that fenofibrate was hydrolyzed to the active drug fenofibric acid already in the stomach. Furthermore, the presence of lyso-phosphatidylcholine (lyso-PC) and taurocholate was confirmed in the lumen of the small intestine. MALDI-MSI was shown to be a useful qualitative tool for localizing parent prodrugs and active drugs, with a possibility for gaining insight into not only the location for activation but also the role of endogenous molecules in the process.

Original languageEnglish
JournalMolecular Pharmaceutics
Volume18
Issue number6
Pages (from-to)2189–2197
ISSN1543-8384
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

Keywords

  • bile salts
  • drug distribution
  • fenofibrate
  • in vivo
  • MALDI-MSI
  • mass spectrometry imaging
  • phospholipids
  • prodrug
  • tissue

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