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 tissuemore » 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.« less

Authors:

Kertesz, Vilmos  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-0186-5797"

Cahill, John F.  ^[1];

• Search DOE PAGES for author "Cahill, John F."
• Search DOE PAGES for ORCID "0000-0002-9866-4010"

Srijanto, Bernadeta R.  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-1188-1267"

Collier, Charles P.  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-8198-793X"

Vavrek, Marissa  ^[2];

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• Search DOE PAGES for ORCID "0000-0003-0240-2583"

Chen, Bingming  ^[2]

• Search DOE PAGES for author "Chen, Bingming"
• Search DOE PAGES for ORCID "0000-0003-3573-4541"

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+ Show Author Affiliations

1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
2. Merck & Co., Inc, Kenilworth, NJ (United States)

Publication Date:

Wed Nov 24 00:00:00 EST 2021

Research Org.:

Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:

1760112

Alternate Identifier(s):

OSTI ID: 1786626

Grant/Contract Number:  

AC05-00OR22725

Resource Type:

Accepted Manuscript

Journal Name:

Rapid Communications in Mass Spectrometry

Additional Journal Information:

Journal Volume: 35; Journal Issue: 5; Journal ID: ISSN 0951-4198

Publisher:

Wiley

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES