Determination of PA-824 in Rat Plasma by HPLC-MS/MS and Application in Pharmaco-kinetic Study / 医药导报
Herald of Medicine
; (12): 1146-1149, 2015.
Artículo
en Chino
| WPRIM (Pacífico Occidental)
| ID: wpr-476605
Biblioteca responsable:
WPRO
ABSTRACT
Objective To develop an HPLC-MS/ MS method for quantitative determination of PA-824 in rat plasma and to study the pharmacokinetics of PA-824 in rat after oral administration. Methods An HPLC-MS/ MS method was developed and validated for determination of PA-824 in rat plasma using metronidazole as internal standard.The proteins in plasma samples were precipitated with methanol,and PA-824 was enriched for analysis by HPLC-MS/ MS.An Inertsil? ODS3 C18 column (150 mm×4.6 mm,5 μm) was applied with mobile phase composed of methanol- 0.03% triethylamine (TEA) in water (9010) ,at a flow rate of 0. 5 mL ? min-1 and column temperature of 30 ℃ . Quantitation was performed on a triple quadrupole mass spectrometer applying electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode with transitions at 360.1/ 175.0 for PA-824 and 172.0/ 128.0 for metronidazole.The concentration of PA-824 in plasma was tested after oral administration at various time points and the data were processed with software DAS.2.0. Results The standard calibration curve for spiked rat plasma containing PA-824 was linear over the range of 0. 1 - 10. 0 μg?mL-1 . The recoveries obtained for PA-824 were greater than 92.13%.Intra-day and inter-day coefficient of variation were less than 6.6%.After oral administration,the main pharmacokinetic parameters were AUC(0-t) ( 3 297. 503 ± 320. 958) mg ? L-1 ? min-1 , AUC(0-∞ )(3 558.315±338.860)mg?L-1?min-1 ,tmax(360.000±64.143)min,Cmax(3.5±0.3)μg?mL-1 . Conclusion The method is rapid,accurate,simple,and successfully applied in a pharmacokinetic study of fixed dose oral administration of PA-824 in rats.
Texto completo:
Disponible
Base de datos:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
Herald of Medicine
Año:
2015
Tipo del documento:
Artículo