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

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

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

Journal Article · Wed Nov 24 00:00:00 EST 2021 · Rapid Communications in Mass Spectrometry

DOI:https://doi.org/10.1002/rcm.9010· OSTI ID:1760112

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

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 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 with positive ion mode electrospray ionization tandem mass spectrometry. Quantitation was achieved via application of a stable isotope-labeled internal standard and an external calibration curve.Results: Absolute concentration of propranolol determined from 200 × 200 µm tissue regions were compared to 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. Average concentration of propranolol in both organs determined by the two employed methods agreed within ±12%. Furthermore, the relative abundance of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results.Conclusions: This work illustrates that depositing a thin parylene C layer 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.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1760112

Alternate ID(s):: OSTI ID: 1786626

Journal Information:: Rapid Communications in Mass Spectrometry, Journal Name: Rapid Communications in Mass Spectrometry Journal Issue: 5 Vol. 35; ISSN 0951-4198

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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