Comparison of a two-dimensional liquid chromatography/mass spectrometry approach with a chip-based nanoelectrospray device for structural elucidation of metabolites in a human ADME study using a quadrupole time-of-flight mass spectrometer.
Rapid Commun Mass Spectrom
; 21(6): 937-44, 2007.
Article
en En
| MEDLINE
| ID: mdl-17295360
ABSTRACT
The study of the metabolic fate of drugs is essential for the safety assessment of new compounds in the drug development process. However, the characterization and structural elucidation of metabolites from in vivo experiments is still a very challenging task. In this paper, we compare a two-dimensional liquid chromatography/mass spectrometry (LC/MS) approach using either a capillary LC/MS system or the recently introduced chip-based nanoelectrospray/MS system (Nanomate) as the second dimension for structural elucidation of metabolites by MS. More than 30 radioactive fractions of a chromatographic separation from a human urine sample were analyzed and 54 metabolites could be identified. The long persisting and stable nanoelectrospray enabled the search for unknown metabolites by precursor-ion scanning experiments followed by product-ion scanning experiments of potential metabolites using a quadrupole time-of-flight (qTOF) mass spectrometer. The number of fragments produced by nanoelectrospray with product-ion scanning was significantly higher compared to LC/MS experiments with in-source fragmentation. Therefore, the assignment of possible modifications in metabolites to certain moieties of the drug could be investigated with higher accuracy. The capillary LC/MS system for the second dimension was more sensitive in the case of low abundant metabolites. These metabolites could not be detected by direct nanoelectrospray infusion, which limits the application of the Nanomate for trace metabolites.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Electroforesis en Gel Bidimensional
/
Cromatografía Líquida de Alta Presión
/
Urinálisis
/
Espectrometría de Masa por Ionización de Electrospray
/
Nanotecnología
/
Dispositivos Laboratorio en un Chip
Tipo de estudio:
Diagnostic_studies
/
Evaluation_studies
/
Prognostic_studies
Idioma:
En
Revista:
Rapid Commun Mass Spectrom
Año:
2007
Tipo del documento:
Article
País de afiliación:
Suiza