title: Online, Absolute Quantitation of Propranolol from Spatially Distinct 20- and 40-μm Dissections of Brain, Liver, and Kidney Thin Tissue Sections by Laser Microdissection-Liquid Vortex Capture-Mass Spectrometry.
abstract: Spatial resolved quantitation of chemical species in thin tissue sections by mass spectrometric methods has been constrained by the need for matrix-matched standards or other arduous calibration protocols and procedures to mitigate matrix effects (e.g., spatially varying ionization suppression). Reported here is the use of laser "cut and drop" sampling with a laser microdissection-liquid vortex capture electrospray ionization tandem mass spectrometry (LMD-LVC/ESI-MS/MS) system for online and absolute quantitation of propranolol in mouse brain, kidney, and liver thin tissue sections of mice administered with the drug at a 7.5 mg/kg dose, intravenously. In this procedure either 20 μm × 20 μm or 40 μm × 40 μm tissue microdissections were cut and dropped into the flowing solvent of the capture probe. During transport to the ESI source drug related material was completely extracted from the tissue into the solvent, which contained a known concentration of propranolol-d7 as an internal standard. This allowed absolute quantitation to be achieved with an external calibration curve generated from standards containing the same fixed concentration of propranolol-d7 and varied concentrations of propranolol. Average propranolol concentrations determined with the laser "cut and drop" sampling method closely agreed with concentration values obtained from 2.3 mm diameter tissue punches from serial sections that were extracted and quantified by HPLC/ESI-MS/MS measurements. In addition, the relative abundance of hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous findings.
authors.affiliation: Mass Spectrometry and Laser Spectroscopy Group, Chemical Sciences Division, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831-6131, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Cahill
authors.affiliation: Mass Spectrometry and Laser Spectroscopy Group, Chemical Sciences Division, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831-6131, United States.
authors.forename: Vilmos
authors.initials: V
authors.lastname: Kertesz
authors.affiliation: ORISE HERE Intern, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Taylor M
authors.initials: TM
authors.lastname: Weiskittel
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , West Point, Pennsylvania 19486, United States.
authors.forename: Marissa
authors.initials: M
authors.lastname: Vavrek
authors.affiliation: Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , West Point, Pennsylvania 19486, United States.
authors.forename: Carol
authors.initials: C
authors.lastname: Freddo
authors.affiliation: Mass Spectrometry and Laser Spectroscopy Group, Chemical Sciences Division, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831-6131, United States.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Van Berkel
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D020407:Internet; D007668:Kidney / Q000737:chemistry*; D061346:Laser Capture Microdissection; D008099:Liver / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D011433:Propranolol / Q000032:analysis*
chemical_list: D011433:Propranolol