Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
Zili Guo,
Bianbian Gao,
Miaoliang Fan,
Lisha Chen,
Changjun Zhang,
Xianrui Liang,
Weike Su,
Yuanyuan Xie
Affiliations
Zili Guo
College 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, China
Bianbian Gao
College 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, China
Miaoliang Fan
College 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, China
Lisha Chen
College 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, China
Changjun Zhang
College 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, China
Xianrui Liang
College 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, China
Weike Su
College 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, China
Yuanyuan Xie
College 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, China
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 (Tmax, 0.57–0.93 h) and then eliminated slowly (T1/2, 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.
