Absolute quantitation of propranolol from 200-µm regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry.
Rapid Commun Mass Spectrom
; 35(5): e9010, 2021 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-33232548
ABSTRACT
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 is 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/tandem mass spectrometry (HPLC/MS/MS) in positive electrospray ionization mode. Quantitation was achieved via application of a stable-isotope-labeled internal standard and an external calibration curve.RESULTS:
The absolute concentrations of propranolol determined from 200 × 200 µm tissue regions were compared with the 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. The average concentration of propranolol in both organs determined by the two employed methods agreed to within ±12%. Furthermore, the relative abundances of phase II hydroxypropranolol glucuronide metabolites were recorded and found to be consistent with previous results.CONCLUSIONS:
This work illustrates that depositing a thin layer of parylene C 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propranolol
/
Química Encefálica
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Cromatografia Líquida de Alta Pressão
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Espectrometria de Massas em Tandem
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Terapia a Laser
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Fígado
Tipo de estudo:
Evaluation_studies
Limite:
Animals
Idioma:
En
Revista:
Rapid Commun Mass Spectrom
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos