Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.
Bioanalysis
; 2(3): 407-19, 2010 Mar.
Article
en En
| MEDLINE
| ID: mdl-21083251
ABSTRACT
BACKGROUND:
The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen.RESULTS:
Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses.CONCLUSION:
LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cromatografía Liquida
/
Espectrometría de Masas en Tándem
/
Metaboloma
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Bioanalysis
Año:
2010
Tipo del documento:
Article