Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug quantitation, metabolite detection, and distribution in tissue

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

doi:10.1002/rcm.9202

Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug quantitation, metabolite detection, and distribution in tissue

Journal Article · Mon Sep 20 00:00:00 EDT 2021 · Rapid Communications in Mass Spectrometry

DOI:https://doi.org/10.1002/rcm.9202· OSTI ID:1826026

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

Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. In this work, application of an integrated laser ablation-dropletProbe-mass spectrometry surface sampling system (LADP-MS) is reported, which achieved absolute quantitation of propranolol measured from <500 × 500 μm thin tissue samples. Methods: Mouse liver and kidney thin tissue sections were coated with parylene C and analyzed for propranolol by a laser ablation/liquid extraction workflow. Non-coated adjacent sections were microdissected for validation and processed using standard bulk tissue extraction protocols. High-performance liquid chromatography with positive ion mode electrospray ionization tandem mass spectrometry was applied to detect the drug and its metabolites. Results: Absolute propranolol concentration in ~500 × 500 μm tissue regions measured by the two methods agreed within ±8% and had a relative standard deviation within ±17%. Quantitation down to ~400 × 400 μm tissue regions was shown, and this resolution was also used for automated mapping of propranolol and phase II hydroxypropranolol glucuronide metabolites in kidney tissue. Conclusions: This study exemplifies the capabilities of integrated laser ablation-dropletProbe-mass spectrometry (LADP-MS) for high resolution absolute drug quantitation analysis of thin tissue sections. This capability will be valuable for applications needing to quantitatively understand the spatial distribution of small molecules in tissue.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1826026

Alternate ID(s):: OSTI ID: 1825196

Journal Information:: Rapid Communications in Mass Spectrometry, Journal Name: Rapid Communications in Mass Spectrometry Journal Issue: 23 Vol. 35; ISSN 0951-4198

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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