title: 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.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Line Rørbæk
authors.initials: LR
authors.lastname: Olsen
authors.forename: Steen Honoré
authors.initials: SH
authors.lastname: Hansen
authors.forename: Christian
authors.initials: C
authors.lastname: Janfelt
mesh_terms: D000825:Animal Structures / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D006110:Grasshoppers; D006633:Histamine Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D016593:Terfenadine / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D006633:Histamine Antagonists; D016593:Terfenadine