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.

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Tytuł:: 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.
Autorzy:: Zhou BC; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Tian YG; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China.
Sun YN; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China.
Liu YL; College of Pharmaceutical Science, Soochow University, Suzhou, China.
Zhao D; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China.; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Źródło:: Biomedical chromatography : BMC [Biomed Chromatogr] 2022 Oct; Vol. 36 (10), pp. e5450. Date of Electronic Publication: 2022 Aug 01.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 1990- : Chichester : Wiley
Original Publication: London : Heyden & Son, c1986-1990
MeSH Terms:: Chromatography, High Pressure Liquid*/methods
Colitis, Ulcerative*/chemically induced
Colitis, Ulcerative*/drug therapy
Tandem Mass Spectrometry*/methods
Acetic Acid ; Animals ; Interleukin-6/metabolism ; Rats ; Tumor Necrosis Factor-alpha/metabolism
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Grant Information:: 222102310375 Henan Province science and technology key projects Fund; MP2021-14 Henan University of Chinese Medicine In-school Support projects Fund
Contributed Indexing:: Keywords: PK/PD; UPLC-MS/MS; hederasaponin C; ulcerative colitis
Substance Nomenclature:: 0 (Interleukin-6)
0 (Tumor Necrosis Factor-alpha)
Q40Q9N063P (Acetic Acid)
Entry Date(s):: Date Created: 20220714 Date Completed: 20220913 Latest Revision: 20220921
Update Code:: 20240104
DOI:: 10.1002/bmc.5450
PMID:: 35831969
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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 C 18 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-1β (IL-1β) in colon tissues were measured using an ELISA assay. The levels of TNF-α, IL-1β 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.
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