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

Kertesz, Vilmos; Vavrek, Marissa; Freddo, Carol; Van Berkel, Gary J.; Cahill, John F.; Weiskittel, Taylor M.

doi:10.1021/acs.analchem.6b01155

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

Journal Article · Mon May 23 00:00:00 EDT 2016 · Analytical Chemistry

DOI:https://doi.org/10.1021/acs.analchem.6b01155· OSTI ID:1261563

Kertesz, Vilmos ^[1]; Vavrek, Marissa ^[2]; Freddo, Carol ^[2]; Van Berkel, Gary J. ^[1]; Cahill, John F. ^[1]; Weiskittel, Taylor M. ^[3]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Merck Research Laboratories, West Point, PA (United States)
Univ. of Tennessee, Knoxville, TN (United States)

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.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC); Work for Others (WFO)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1261563

Journal Information:: Analytical Chemistry, Vol. 88, Issue 11; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 31 works

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