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

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

doi:10.1002/rcm.9202

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

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

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

1 Scopus citations

Abstract

Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. Here, 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.

Original language	English
Article number	e9202
Journal	Rapid Communications in Mass Spectrometry
Volume	35
Issue number	23
DOIs	https://doi.org/10.1002/rcm.9202
State	Published - 2021

Funding

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 Technology Transfer Maturation Program of Oak Ridge National Laboratory, managed by UT‐Battelle, LLC, for the U.S. Department of Energy. The parylene C coating (B.R.S. and C.P.C.) was conducted at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility. Software package dropletProbe Premium© was previously developed with support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division. Amber Webb (Biosciences Division, Oak Ridge National Laboratory) is thanked for help taking the high‐resolution optical images of the tissue slides. 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 Technology Transfer Maturation Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy. The parylene C coating (B.R.S. and C.P.C.) was conducted at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility. Software package dropletProbe Premium? was previously developed with support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division. Amber Webb (Biosciences Division, Oak Ridge National Laboratory) is thanked for help taking the high-resolution optical images of the tissue slides. 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
U.S. Department of Energy
Merck
Office of Science
Basic Energy Sciences
Oak Ridge National Laboratory
Chemical Sciences, Geosciences, and Biosciences Division

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

abstract = "Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. Here, 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.",

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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year = "2021",

doi = "10.1002/rcm.9202",

language = "English",

volume = "35",

journal = "Rapid Communications in Mass Spectrometry",

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AU - Kertesz, Vilmos

AU - Cahill, John F.

AU - Srijanto, Bernadeta R.

AU - Collier, Charles P.

AU - Vavrek, Marissa

AU - Chen, Bingming

PY - 2021

Y1 - 2021

N2 - Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. Here, 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.

AB - Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. Here, 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.

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

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