Distribution of terfenadine and its metabolites in locusts studied by desorption electrospray ionization mass spectrometry imaging

Abstract

Desorption electrospray ionization (DESI) mass spectrometry (MS) imaging was used to image locusts dosed with the antihistamine drug terfenadine. The study was conducted in order to elucidate a relatively high elimination rate of terfenadine from the locust hemolymph. In this one of the few MS imaging studies on insects, a method for cryosectioning of whole locusts was developed, and the distributions of a number of endogenous compounds are reported, including betaine and a number of amino acids and phospholipids. Terfenadine was detected in the stomach region and the intestine walls, whereas three different metabolites-terfenadine acid (fexofenadine), terfenadine glucoside, and terfenadine phosphate-were detected in significantly smaller amounts and only in the unexcreted feces in the lower part of the intestine. The use of MS/MS imaging was necessary in order to detect the metabolites. With use of DESI-MS imaging, no colocalization of the drug and the metabolites was observed, suggesting a very rapid excretion of metabolites into the feces. Additional liquid chromatography-MS investigations were performed on hemolymph and feces and showed some abundance of terfenadine and the three metabolites, although at low levels, in both the hemolymph and the feces.

Review and perspectives on the applications of mass spectrometry imaging under ambient conditions

“…The full scan MS data allowed the visualization of endogenous phospholipids, while the drug and its metabolites were imaged in MS/MS mode. This sensitive targeted approach in whole‐body tissue imaging allows the general overview of endogenous molecules sampled in full scan mode and simultaneously delivers the required sensitivity to image low‐abundance small molecules in MS/MS mode …”

Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

“…150 Because of its blood-brain barrier similarities with mammals, the locust has been evaluated as a future model species for drug development. 151 Using DESI MSI, terfenadine and its metabolite terfenadine acid were mapped in the whole body of a locust. 151 Interestingly, the ion images of the drug and its metabolite did not correlate.…”

“…151 Using DESI MSI, terfenadine and its metabolite terfenadine acid were mapped in the whole body of a locust. 151 Interestingly, the ion images of the drug and its metabolite did not correlate. The metabolite was only detected in unexcreted feces, suggesting an immediate delocalization of the metabolite upon formation.…”

Mass spectrometry imaging: An emerging technology for the analysis of metabolites in insects

“…MSI has been applied to insect tissue section for in situ characterization of three major aspects, endogenous metabolites (including lipids, neuropeptides, proteins, and defense compounds; Bhandari, Schott, Römpp, Vilcinskas, & Spengler, ; Catae et al, ; Ly et al, ; Marty et al, ), exogenous metabolites (drugs and insecticides; Ohtsu, Yamaguchi, Nishiwaki, Fukusaki, & Shimma, ; Olsen, Hansen, & Janfelt, ), and insect–plant interactions (tracking the fate of plant secondary defense compounds; Crecelius, Michalzik, Potthast, Meyer, & Schubert, ). How insects rapidly adapt to host plant, how insects are resistant to insecticides, and how insects interact with gut microbes have recently become hot topics in insect sciences.…”