title: MALDI-tandem mass spectrometry imaging of astemizole and its primary metabolite in rat brain sections.
abstract: BACKGROUND
  Matrix-assisted laser desorption/ionization (MALDI)-tandem mass spectrometry (MS)/MS is a proven reliable tool for visualizing the spatial distribution of dosed drugs and their primary metabolites in animal tissue sections.
  
  
  METHODS
  The rat brain tissue sections coated with dihydroxybenzoic acid as matrix, were analyzed by MALDI-MS/MS imaging experiments. The potential metabolites of astemizole in rat brain homogenate selected for MALDI-MS/MS imaging experiments were first identified by high-performance liquid chromatography coupled to an electrospray ionization source and a hybrid-quadrupole-linear-ion-trap mass spectrometer.
  
  
  RESULTS
  Astemizole was observed to be heterogeneously distributed to most parts of the brain tissue slices including the cortex, hippocampus, hypothalamic, thalamus and ventricle regions, while its major metabolite, desmethylastemizole, was only found around ventricle sites.
  
  
  CONCLUSIONS
  The results indicated that the dosed compound alone might be responsible for the CNS side-effects when drug exposures became elevated.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3700, Kenilworth, NJ 07033, USA.
authors.forename: Fangbiao
authors.initials: F
authors.lastname: Li
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Hsieh
authors.forename: Ling
authors.initials: L
authors.lastname: Kang
authors.forename: Christopher
authors.initials: C
authors.lastname: Sondey
authors.forename: Jean
authors.initials: J
authors.lastname: Lachowicz
authors.forename: Walter A
authors.initials: WA
authors.lastname: Korfmacher
mesh_terms: D000818:Animals; D016589:Astemizole / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D001923:Brain Chemistry; D002552:Cerebral Ventricles / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003952:Diagnostic Imaging; D039563:Histamine H1 Antagonists, Non-Sedating / Q000032:analysis / Q000097:blood* / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D016589:Astemizole; C040463:desmethylastemizole