High-throughput quantitative and qualitative analysis of microsomal incubations by cocktail analysis with an ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometer system.
Bioanalysis
; 7(6): 671-83, 2015.
Article
em En
| MEDLINE
| ID: mdl-25517264
ABSTRACT
BACKGROUND:
Metabolite identification studies are very resource intensive and also are rarely performed in early discovery. Here, we report the validation of an ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) platform for generating high-throughput stability data with structure elucidation in a single injection. MATERIALS &METHODS:
Tandem mass spectrometry spectra were obtained for quantitative analysis using a generic information-dependent acquisition method from pooled microsomal samples incubated at low compound concentrations.RESULTS:
A good correlation was observed between clearance determined using UPLC-HRMS and UPLC-triple-quadrupole analysis. Structural elucidation performed with MassMetaSite™ (Molecular Discovery, Perugia, Italy) software identified 85% of the major metabolites of eight marketed drugs and over 100 internal compounds under these conditions.CONCLUSION:
For the first time, a high-throughput quantitative-qualitative workflow was established using a cocktail approach for sample analysis with UPLC-HRMS in order to enable metabolite identification in early discovery projects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microssomos Hepáticos
/
Metabolômica
Tipo de estudo:
Qualitative_research
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article