Absolute quantitation of propranolol from 200-μm regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry

Vilmos Kertesz; John F. Cahill; Bernadeta R. Srijanto; Charles P. Collier; Marissa Vavrek; Bingming Chen

doi:10.1002/rcm.9010

Absolute quantitation of propranolol from 200-μm regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry

Vilmos Kertesz, John F. Cahill, Bernadeta R. Srijanto, Charles P. Collier, Marissa Vavrek, Bingming Chen

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Rationale: The ability to quantify drugs and metabolites in tissue with sub-mm resolution is a challenging but much needed capability in pharmaceutical research. To fill this void, a novel surface sampling approach combining laser ablation with the commercial dropletProbe automated liquid surface sampling system (LA-dropletProbe) was developed and is presented here. Methods: Parylene C-coated 200 × 200 μm tissue regions of mouse brain and kidney thin tissue sections were analyzed for propranolol by laser ablation of tissue directly into a preformed liquid junction. Propranolol was detected by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) in positive electrospray ionization mode. Quantitation was achieved via application of a stable-isotope-labeled internal standard and an external calibration curve. Results: The absolute concentrations of propranolol determined from 200 × 200 μm tissue regions were compared with the propranolol concentrations obtained from 2.3-mm-diameter tissue punches of adjacent, non-coated sections using standard bulk tissue extraction protocols followed by regular HPLC/MS/MS analysis. The average concentration of propranolol in both organs determined by the two employed methods agreed to within ±12%. Furthermore, the relative abundances of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results. Conclusions: This work illustrates that depositing a thin layer of parylene C onto thin tissue prior to analysis, which seals the surface and prevents direct liquid extraction of the drug from the tissue, coupled to the novel LA-dropletProbe surface sampling system is a viable approach for sub-mm resolution quantitative drug distribution analysis.

Original language	English
Article number	e9010
Journal	Rapid Communications in Mass Spectrometry
Volume	35
Issue number	5
DOIs	https://doi.org/10.1002/rcm.9010
State	Published - Mar 15 2021

Funding

U.S. Department of Energy, Office of Science, Biological and Environmental Research, Bioimaging Science Program; Oak Ridge National Laboratory, Grant/Award Number: Laboratory Directed Research and Development Program Funding information The work of V.K. and J.F.C. was supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research, Bioimaging Science Program and by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy. The parylene C coating procedures (B.R.S. and C.P.C.) were performed at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility and sponsored at Oak Ridge National Laboratory by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. The 5500 QTRAP instrument used in this work was provided on loan from Sciex. Software packages LMD Assistant? and dropletProbe Premium? were previously developed with support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division. Matthew S. Orcutt (Resolution Labs, LLC, New Haven, IN, USA) is thanked for discussions on the operation of the dropletProbe system. Scott Fauty and Lisa LaFranco-Scheuch (Department of Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., Kenilworth, NJ, USA) are thanked for performing animal experiments and discussing mouse brain anatomy, respectively. The work of V.K. and J.F.C. was supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research, Bioimaging Science Program and by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT‐Battelle, LLC, for the U.S. Department of Energy. The parylene C coating procedures (B.R.S. and C.P.C.) were performed at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility and sponsored at Oak Ridge National Laboratory by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. The 5500 QTRAP instrument used in this work was provided on loan from Sciex. Software packages LMD Assistant© and dropletProbe Premium© were previously developed with support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division. Matthew S. Orcutt (Resolution Labs, LLC, New Haven, IN, USA) is thanked for discussions on the operation of the dropletProbe system. Scott Fauty and Lisa LaFranco‐Scheuch (Department of Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., Kenilworth, NJ, USA) are thanked for performing animal experiments and discussing mouse brain anatomy, respectively.

Funders	Funder number
Department of Safety Assessment and Laboratory Animal Resources
Scientific User Facilities Division
U.S. Department of Energy
Merck
Office of Science
Basic Energy Sciences
Oak Ridge National Laboratory
Laboratory Directed Research and Development
Chemical Sciences, Geosciences, and Biosciences Division

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10.1002/rcm.9010

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title = "Absolute quantitation of propranolol from 200-μm regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry",

abstract = "Rationale: The ability to quantify drugs and metabolites in tissue with sub-mm resolution is a challenging but much needed capability in pharmaceutical research. To fill this void, a novel surface sampling approach combining laser ablation with the commercial dropletProbe automated liquid surface sampling system (LA-dropletProbe) was developed and is presented here. Methods: Parylene C-coated 200 × 200 μm tissue regions of mouse brain and kidney thin tissue sections were analyzed for propranolol by laser ablation of tissue directly into a preformed liquid junction. Propranolol was detected by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) in positive electrospray ionization mode. Quantitation was achieved via application of a stable-isotope-labeled internal standard and an external calibration curve. Results: The absolute concentrations of propranolol determined from 200 × 200 μm tissue regions were compared with the propranolol concentrations obtained from 2.3-mm-diameter tissue punches of adjacent, non-coated sections using standard bulk tissue extraction protocols followed by regular HPLC/MS/MS analysis. The average concentration of propranolol in both organs determined by the two employed methods agreed to within ±12%. Furthermore, the relative abundances of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results. Conclusions: This work illustrates that depositing a thin layer of parylene C onto thin tissue prior to analysis, which seals the surface and prevents direct liquid extraction of the drug from the tissue, coupled to the novel LA-dropletProbe surface sampling system is a viable approach for sub-mm resolution quantitative drug distribution analysis.",

author = "Vilmos Kertesz and Cahill, {John F.} and Srijanto, {Bernadeta R.} and Collier, {Charles P.} and Marissa Vavrek and Bingming Chen",

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AU - Kertesz, Vilmos

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AU - Srijanto, Bernadeta R.

AU - Collier, Charles P.

AU - Vavrek, Marissa

AU - Chen, Bingming

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N2 - Rationale: The ability to quantify drugs and metabolites in tissue with sub-mm resolution is a challenging but much needed capability in pharmaceutical research. To fill this void, a novel surface sampling approach combining laser ablation with the commercial dropletProbe automated liquid surface sampling system (LA-dropletProbe) was developed and is presented here. Methods: Parylene C-coated 200 × 200 μm tissue regions of mouse brain and kidney thin tissue sections were analyzed for propranolol by laser ablation of tissue directly into a preformed liquid junction. Propranolol was detected by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) in positive electrospray ionization mode. Quantitation was achieved via application of a stable-isotope-labeled internal standard and an external calibration curve. Results: The absolute concentrations of propranolol determined from 200 × 200 μm tissue regions were compared with the propranolol concentrations obtained from 2.3-mm-diameter tissue punches of adjacent, non-coated sections using standard bulk tissue extraction protocols followed by regular HPLC/MS/MS analysis. The average concentration of propranolol in both organs determined by the two employed methods agreed to within ±12%. Furthermore, the relative abundances of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results. Conclusions: This work illustrates that depositing a thin layer of parylene C onto thin tissue prior to analysis, which seals the surface and prevents direct liquid extraction of the drug from the tissue, coupled to the novel LA-dropletProbe surface sampling system is a viable approach for sub-mm resolution quantitative drug distribution analysis.

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Absolute quantitation of propranolol from 200-μm regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry

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