title: MALDI imaging mass spectrometry: bridging biology and chemistry in drug development.
abstract: Our understanding of drug tissue distribution impacts a number of areas in drug development, including: pharmacology, pharmacokinetics, safety, drug-drug interactions, transport and metabolism. Despite their extensive use, autoradiography and tissue homogenate LC-MS analysis have limitations in providing a comprehensive assessment of tissue distributions. In the case of autoradiography, it is the inability to distinguish between parent drug and drug metabolites. In LC-MS analysis of tissue homogenate, all tissue localization information is lost. The emerging technique of MALDI imaging mass spectrometry has the capability to distinguish between parent and metabolites while maintaining spatial distribution in tissues. In this article, we will review the MALDI imaging MS methodology as applied to drug development and provide examples highlighting the impact of this important technique in drug development.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Platform Science & Technology, GlaxoSmithKline, RTP, NC 27709, USA. steve.x.castellino@gsk.com
authors.forename: Stephen
authors.initials: S
authors.lastname: Castellino
authors.forename: M Reid
authors.initials: MR
authors.lastname: Groseclose
authors.forename: David
authors.initials: D
authors.lastname: Wagner
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000295:instrumentation / Q000379:methods; D004347:Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations