Pharmacokinetics and blood-brain barrier penetration of (+)-catechin and (-)-epicatechin in rats by microdialysis sampling coupled to high-performance liquid chromatography with chemiluminescence detection.

(+)-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 (AUC(brain)/AUC(blood)) 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.