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Pharmacokinetics and tissue distribution study of hupehenenine in rats: A novel isosteroid alkaloid isolated from Bulbus Hupehensis Fritillariae
Author(s) -
Zhang Qinyan,
Li Dongguo,
Ma Bihua,
Wang Xueyan,
Yang Junyi,
Chen Donglin,
Ye Liming
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.5122
Subject(s) - alkaloid , pharmacokinetics , chemistry , chromatography , high performance liquid chromatography , in vitro , analyte , detection limit , pharmacology , biochemistry , biology , stereochemistry
Abstract Hupehenenine is a novel isosteroid alkaloid that was first isolated from Bulbus Hupehensis Fritillariae . The inhibitory proliferation effect of hupehenenine and its three related alkaloid derivatives, including o ‐caproyl‐hupehenenine, o ‐(2‐furanoyl)‐hupehenenine, and Δ 5(6) ‐isopeimine on human lung cancer cell line, human chronic myeloid leukemia cell line, and human thyroid duct cancer cell line in vitro , has been identified. This study first developed a sensitive HPLC‐MS/MS method for the simultaneous quantification of hupehenenine and three alkaloid derivatives in rat plasma and tissues. The developed method was validated, and it was linear over the concentration range of 1–800 ng/mL for all analytes with R 2 ≥ 0.9939 and 0.9972, respectively, in rat plasma and rat liver homogenate. The lower limit of quantitation was 1 ng/mL for all analytes. The intra‐day and inter‐day precision and accuracy were satisfactory. This validated method was successfully applied to investigate the pharmacokinetics and tissue distribution of hupehenenine in rats. In pharmacokinetic study, the maximum plasma concentration of rats exists gender difference. Tissue distribution study showed that hupehenenine has good affinity for multiple tissues but is unable to cross the blood–brain barrier. These results may provide a useful reference for further research of hupehenenine and its three related alkaloid derivatives.