Application of DBS sampling in combination with LC-MS/MS for pharmacokinetic evaluation of a compound with species-specific blood-to-plasma partitioning.
Bioanalysis
; 4(16): 2037-47, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22946919
ABSTRACT
BACKGROUND:
Dried blood spot (DBS) sampling in combination with LC-MS/MS has been used increasingly in drug discovery for quantitative analysis to support pharmacokinetic (PK) studies. In this study, we assessed the effect of blood-to-plasma (BP) partitioning on the bioanalytical performance and PK data acquired by DBS for a compound AMG-1 with species and concentration-dependent BP ratio.RESULTS:
BP partitioning did not adversely affect bioanalytical performance of DBS for AMG-1. For rat, (BP ratio of 0.63), PK profiles from DBS and plasma methods were comparable. For dog, concentration-dependence of BP ratio was observed both in vivo and in vitro. Additional studies demonstrated concentration-dependence of the compound's unbound fraction in plasma, which may contribute to the concentration-dependence of the BP ratio.CONCLUSION:
DBS is a promising sampling technique for preclinical pharmacokinetic studies. For compounds with high BP ratio, caution needs to be applied for data comparison and interpretation between matrices.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacocinética
/
Preparaciones Farmacéuticas
/
Pruebas con Sangre Seca
Tipo de estudio:
Evaluation_studies
Límite:
Animals
Idioma:
En
Revista:
Bioanalysis
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos