Pharmacokinetics and Blood–Brain Barrier Penetration of (+)-Catechin and (−)-Epicatechin in Rats by Microdialysis Sampling Coupled to High-Performance Liquid Chromatography with Chemiluminescence Detection

• Published in: Journal of agricultural and food chemistry Vol. 60; no. 37; pp. 9377 - 9383
• Main Authors: Wu, Liang, Zhang, Qun-Lin, Zhang, Xiao-Yue, Lv, Chen, Li, Jun, Yuan, Ye, Yin, Fang-Xiong
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 19-09-2012
• Subjects: Animals; Biological and medical sciences; blood; Blood-Brain Barrier - metabolism; body weight; brain; Catechin - administration & dosage; Catechin - pharmacokinetics; chemiluminescence; Chromatography, High Pressure Liquid - methods; detection limit; Drug Stability; flavanols; Food industries; Fundamental and applied biological sciences. Psychology; General aspects; high performance liquid chromatography; intravenous injection; Luminescent Measurements - methods; Male; medicinal plants; Methods of analysis, processing and quality control, regulation, standards; Microdialysis; Neuroprotective Agents - pharmacokinetics; neuroprotective effect; pharmacokinetics; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; pharmacokinetics; blood−brain barrier; microdialysis; (−)-epicatechin; (+)-catechin; Flavanol; Catechin; Rat; Rodentia; Samplings; (—)—epicatechin; HPLC chromatography; Chemiluminescence; Flavonoid; Blood; blood―brain barrier; Polyphenol; Vertebrata; Mammalia; Analysis method; Penetration; Control method; Detection; Sampling; Pharmacokinetics
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf301787f

(+)-Catechin (C) and (−)-epicatechin (EC), as the basic monomer units of flavanols, can be widely found in natural products or medicinal herbs. Recent pharmacological studies have revealed that C and EC exhibit good neuroprotective effects. However, there is little information about pharmacokinetic profiles in the brain and in vivo BBB penetration of C and EC. In this paper, an ultrasensitive method using high-performance liquid chromatography (HPLC) with chemiluminescence (CL) detection was developed for the analysis of microdialysis samples. The detection limits for C and EC in Ringer’s solution were 1.0 and 1.2 ng/mL, respectively. The intraday and interday accuracies for C and EC in Ringer’s solution ranged from −3.0 to 4.4%, and the intraday and interday precisions were below 5.2%. The mean in vivo recoveries of C and EC in microdialysis probes were 33.7% and 26.5% in blood while 38.3% and 29.1% in brain. Pharmacokinetic parameters were estimated using the statistical moment method after iv administration (C and EC, 20 mg/kg of body weight) in rats. Brain-to-blood (AUCbrain/AUCblood) distribution ratios were 0.0726 ± 0.0376 for C and 0.1065 ± 0.0531 for EC, indicating that C and EC could pass through the BBB, which is further evidence of their neuroprotective effects.