Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging
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Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging. / Strindberg, Sophie; Plum, Jakob; Bagger, Charlotte; Janfelt, Christian; Müllertz, Anette.
In: Molecular Pharmaceutics, Vol. 18, No. 6, 2021, p. 2189–2197.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging
AU - Strindberg, Sophie
AU - Plum, Jakob
AU - Bagger, Charlotte
AU - Janfelt, Christian
AU - Müllertz, Anette
N1 - Publisher Copyright: © 2021 American Chemical Society.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - bile salts
KW - drug distribution
KW - fenofibrate
KW - in vivo
KW - MALDI-MSI
KW - mass spectrometry imaging
KW - phospholipids
KW - prodrug
KW - tissue
U2 - 10.1021/acs.molpharmaceut.0c01043
DO - 10.1021/acs.molpharmaceut.0c01043
M3 - Journal article
C2 - 33891424
AN - SCOPUS:85106440013
VL - 18
SP - 2189
EP - 2197
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 6
ER -
ID: 273634534