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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

Here, 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 x 20 μm or 40 μm x 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 propranolold-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 tissuemore » 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.« less

Authors:
 [1];  [2];  [2];  [1];  [1];  [3]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Merck Research Laboratories, West Point, PA (United States)
  3. Univ. of Tennessee, Knoxville, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); Work for Others (WFO)
OSTI Identifier:
1261563
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Analytical Chemistry
Additional Journal Information:
Journal Volume: 88; Journal Issue: 11; Journal ID: ISSN 0003-2700
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Kertesz, Vilmos, Vavrek, Marissa, Freddo, Carol, Van Berkel, Gary J., Cahill, John F., and Weiskittel, Taylor M. 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. United States: N. p., 2016. Web. doi:10.1021/acs.analchem.6b01155.
Kertesz, Vilmos, Vavrek, Marissa, Freddo, Carol, Van Berkel, Gary J., Cahill, John F., & Weiskittel, Taylor M. 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. United States. https://doi.org/10.1021/acs.analchem.6b01155
Kertesz, Vilmos, Vavrek, Marissa, Freddo, Carol, Van Berkel, Gary J., Cahill, John F., and Weiskittel, Taylor M. Mon . "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". United States. https://doi.org/10.1021/acs.analchem.6b01155. https://www.osti.gov/servlets/purl/1261563.
@article{osti_1261563,
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},
author = {Kertesz, Vilmos and Vavrek, Marissa and Freddo, Carol and Van Berkel, Gary J. and Cahill, John F. and Weiskittel, Taylor M.},
abstractNote = {Here, 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 x 20 μm or 40 μm x 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 propranolold-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.},
doi = {10.1021/acs.analchem.6b01155},
journal = {Analytical Chemistry},
number = 11,
volume = 88,
place = {United States},
year = {2016},
month = {5}
}

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