Pharmacokinetic study of three different formulations of l-tetrahydropalmatine in brain tissues of rats.
Biomed Chromatogr
; 35(5): e5066, 2021 May.
Article
en En
| MEDLINE
| ID: mdl-33452741
ABSTRACT
l-Tetrahydropalmatine (l-THP), an active alkaloid compound isolated from Rhizoma Corydalis-yanhusuo, has been reported to possess biological activity for treating cocaine use. To enhance both oral bioavailability and brain penetration, three formulations of l-THP suspension, mixture of l-THP-puerarin and self-microemulsifying drug delivery systems (SMEDDS) were prepared. A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of l-THP and its active metabolite l-isocorypalmine (l-ICP) in rat brain. Diazepam was used as the internal standard. The chromatographic separation was achieved on a Bonshell ASB C18 column at 30°C using acetonitrile-aqueous formic acid as mobile phase in gradient mode. The linearity was validated over the concentration ranges of 4.00-2,500 ng/ml for l-THP and 0.400-500 ng/ml for l-ICP. Full method validation was within the acceptance limits. The method was successfully used to determine the pharmacokinetics of two analytes following oral administration of these three formulations to rats. A significant difference was observed in the main pharmacokinetic parameters between SMEDDS and the suspension, and a 3.25- and 2.97-fold increase in the relative bioavailability of l-THP and l-ICP, respectively, was observed with the SMEDDS compared with the suspension formulation. It was concluded that SMEDDS enhanced the absorption of l-THP and l-ICP and delayed their release in brain.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Alcaloides de Berberina
/
Química Encefálica
/
Trastornos Relacionados con Cocaína
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2021
Tipo del documento:
Article
País de afiliación:
China