A validated LC-MS/MS method for the determination of hederasaponin C: Application to pharmacokinetics-pharmacodynamics studies in the therapeutic area of acetic acid-induced ulcerative colitis in rats.
Biomed Chromatogr
; 36(10): e5450, 2022 Oct.
Article
en En
| MEDLINE
| ID: mdl-35831969
ABSTRACT
Hederasaponin C (HSC), one of the main components of Pulsatilla chinensis, is considered as a potential drug for the treatment of inflammatory bowel disease. In the present research, we developed a pharmacokinetics-pharmacodynamics model to describe the concentration-effect course of drug action following the intraperitoneal injection of HSC in colitis rats. A sensitive UPLC-MS/MS method was established for the the determination of HSC in rat plasma to explore the pharmacokinetics properties. The separation was performed on an Accucore C18 column (2.1 × 100 mm, 2.6 µm) with a flow phase consisting of acetonitrile and 0.1% formic acid water. The assay method was validated and demonstrated good adaptability for application in the pharmacokinetics study. Then the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in colon tissues were measured using an ELISA assay. The levels of TNF-α, IL-1ß and IL-6 were decreased after HSC administration, suggesting that HSC can significantly improve the level of inflammatory syndrome factor. The pharmacokinetics study showed that the time to peak concentration of HSC was 1 h. The concentration-effect curves showed a hysteresis loop. There was also a hysteresis between the peaked concentration and the maximum effect of HSC. The present study established in vivo pharmacokinetics-pharmacodynamics models and the results showed a great potential of HSC for treating ulcerative colitis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colitis Ulcerosa
/
Cromatografía Líquida de Alta Presión
/
Espectrometría de Masas en Tándem
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Chromatogr
Año:
2022
Tipo del documento:
Article
País de afiliación:
China