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
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Espectrometria de Massas por Ionização por Electrospray
/
Imagem Molecular
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Rapid Commun Mass Spectrom
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos