title: Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography.
abstract: Desorption electrospray ionization tandem mass spectrometry (DESI-MS/MS) and whole-body autoradiography (WBA) were used for chemical imaging of whole-body thin tissue sections of mice intravenously dosed with propranolol (7.5 mg/kg). DESI-MS/MS imaging utilized selected reaction monitoring detection performed on an AB/MDS SCIEX 4000 QTRAP mass spectrometer equipped with a prototype extended length particle discriminator interface. Propranolol images of the tissue sections using DESI-MS/MS were obtained at surface scan rates of 0.1, 0.5, 2, and 7 mm/s. Although signal decreased with increasing scan rate, useful whole-body images for propranolol were obtained from the tissues even at 7 mm/s, which required just 79 min of analysis time. Attempts to detect and image the distribution of the known propranolol metabolites were unsuccessful. Regions of the tissue sections showing the most radioactivity from WBA sections were excised and analyzed by high-performance liquid chromatography (HPLC) with radiochemical detection to determine relative levels of propranolol and metabolites present. Comparison of the DESI-MS/MS signal for propranolol and the radioactivity attributed to propranolol from WBA sections indicated nominal agreement between the two techniques for the amount of propranolol in the brain, lung, and liver. Data from the kidney showed an unexplained disparity between the two techniques. The results of this study show the feasibility of using DESI-MS/MS to obtain useful chemical images of a drug in whole-body thin tissue sections following drug administration at a pharmacologically relevant level. Further optimization to improve sensitivity and enable detection of the drug metabolites will be among the requirements necessary to move DESI-MS/MS chemical imaging forward as a practical tool in drug discovery.
authors.affiliation: Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6131, USA. kerteszv@ornl.gov
authors.forename: Vilmos
authors.initials: V
authors.lastname: Kertesz
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Van Berkel
authors.forename: Marissa
authors.initials: M
authors.lastname: Vavrek
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Koeplinger
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Schneider
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Covey
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods*; D020719:Glucuronides / Q000032:analysis / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008867:Microtomy / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010599:Pharmacokinetics; D011433:Propranolol / Q000032:analysis / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D020719:Glucuronides; D004364:Pharmaceutical Preparations; D011433:Propranolol