Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS

XYY-CP1106, a candidate compound synthesized from a hybrid of hydroxypyridinone and coumarin, has been shown to be remarkably effective in treating Alzheimer’s disease. A simple, rapid and accurate high-performance liquid chromatography coupled with the triple quadrupole mass spectrometer (LC-MS/MS)...

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Bibliographic Details
Main Authors: Zili Guo, Bianbian Gao, Miaoliang Fan, Lisha Chen, Changjun Zhang, Xianrui Liang, Weike Su, Yuanyuan Xie
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/28/5/2377
Description
Summary:XYY-CP1106, a candidate compound synthesized from a hybrid of hydroxypyridinone and coumarin, has been shown to be remarkably effective in treating Alzheimer’s disease. A simple, rapid and accurate high-performance liquid chromatography coupled with the triple quadrupole mass spectrometer (LC-MS/MS) method was established in this study to elucidate the pharmacokinetics of XYY-CP1106 after oral and intravenous administration in rats. XYY-CP1106 was shown to be rapidly absorbed into the blood (<i>T</i><sub>max</sub>, 0.57–0.93 h) and then eliminated slowly (<i>T</i><sub>1/2</sub>, 8.26–10.06 h). Oral bioavailability of XYY-CP1106 was (10.70 ± 1.72)%. XYY-CP1106 could pass through the blood–brain barrier with a high content of (500.52 ± 260.12) ng/g at 2 h in brain tissue. The excretion results showed that XYY-CP1106 was mainly excreted through feces, with an average total excretion rate of (31.14 ± 0.05)% in 72 h. In conclusion, the absorption, distribution and excretion of XYY-CP1106 in rats provided a theoretical basis for subsequent preclinical studies.
ISSN:1420-3049