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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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
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/5/2377
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author Zili Guo
Bianbian Gao
Miaoliang Fan
Lisha Chen
Changjun Zhang
Xianrui Liang
Weike Su
Yuanyuan Xie
author_facet Zili Guo
Bianbian Gao
Miaoliang Fan
Lisha Chen
Changjun Zhang
Xianrui Liang
Weike Su
Yuanyuan Xie
author_sort Zili Guo
collection DOAJ
description 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.
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spelling doaj.art-39aa218031cd47698c3d0591aa0e5a0b2023-11-17T08:15:51ZengMDPI AGMolecules1420-30492023-03-01285237710.3390/molecules28052377Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MSZili Guo0Bianbian Gao1Miaoliang Fan2Lisha Chen3Changjun Zhang4Xianrui Liang5Weike Su6Yuanyuan Xie7College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, ChinaXYY-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.https://www.mdpi.com/1420-3049/28/5/2377XYY-CP1106Alzheimer’s diseaseLC-MS/MSpharmacokineticstissue distributionexcretion study
spellingShingle Zili Guo
Bianbian Gao
Miaoliang Fan
Lisha Chen
Changjun Zhang
Xianrui Liang
Weike Su
Yuanyuan Xie
Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
Molecules
XYY-CP1106
Alzheimer’s disease
LC-MS/MS
pharmacokinetics
tissue distribution
excretion study
title Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
title_full Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
title_fullStr Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
title_full_unstemmed Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
title_short Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
title_sort study on absorption distribution and excretion of a new candidate compound xyy cp1106 against alzheimer s disease in rats by lc ms ms
topic XYY-CP1106
Alzheimer’s disease
LC-MS/MS
pharmacokinetics
tissue distribution
excretion study
url https://www.mdpi.com/1420-3049/28/5/2377
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