Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug quantitation, metabolite detection, and distribution in tissue.
Rapid Commun Mass Spectrom
; 35(23): e9202, 2021.
Article
en En
| MEDLINE
| ID: mdl-34545636
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
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Espectrometría de Masa por Ionización de Electrospray
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Imagen Molecular
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article