ABSTRACT
Objective: To conduct a comparative study on the brain pharmacokinetics of seven ingredients (i. e. senkyunolide A, ferulic acid, formononetin, calycosin, ononin, calycosin-O-β-D-glucopyranoside, and paeoniflorin), which were the compounds of Buyang Huanwu Decoction (BHD), in normal and cerebral ischemia rats administrated intragastrically with BHD. Methods: The samples of normal and permanent middle cerebral artery occlusion (pMCAO) rats were collected by using brain microdialysis technique. The concentrations of seven ingredients were determined by the HPLC-MS/MS method. After the BHD were administrated intragastrically to the rats for seven consecutive days, brain microdialysis probes were inserted into the hippocampus of rats, and then the brain microdialysates were collected at 20 min time intervals for 5 h. The separation of the seven ingredients and internal standard (IS) was carried out on an ACQUITY UPLC BEH C
ABSTRACT
Objective: To compare the brain pharmacokinetics of five protoberberine-type alkaloids (i.e. berberine, palmatine, coptisine, epiberberine, and jatrorrhizine), which were the main bioactive constituents of Jiaotai Pills (JTP), in normal and insomnic rats orally administrated with JTP. Methods: The detection was conducted by a fully validated liquid chromatography-tandem mass spectrometry combinated with brain microdialysis method. Brain microdialysis probes were inserted into the hippocampus of rats. JTP extracts were administrated intragastrically and then brain microdialysates were collected at 30 min time intervals for 10 h. The separation of the five protoberberine-type alkaloids was carried out on a BDS Hypersil C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0) within 4 min. The quantification was performed by multiple reaction monitoring with the transitions of m/z 336.0-320.1 for berberine, m/z 352.0-336.1 for palmatine, m/z 338.0-322.1 for jatrorrhizine, m/z 336.0-320.1 for epiberberine, m/z 320.0-292.1 for coptisine and m/z 356.4-192.1 for IS. Results: The lower limit of quantification for five protoberberine-type alkaloids was 0.05 ng/mL. Linearity, accuracy, precision, stability and matrix effect of five analytes were all satisfactory. Five protoberberine-type alkaloids were quickly distributed in the brain. Moreover, significant differences in the principal pharmacokinetic parameters such as AUC and T1/2 of the analytes were observed between two groups. Conclusion: The LC-MS/MS method combinated with microdialysis is useful in the brain pharmacokinetic study of five protoberberine-type alkaloids. The results indicated that the rates of analytes absorption in insomnic rats were significantly higher than those in normal rats. Besides, the protoberberine-type alkaloids could bring a direct effect on the neuron in the hippocampus.
ABSTRACT
Aim To prepare NT-Ⅰ loaded nanoparticles with different diameters modified by Methylated-polyethyleneglycol (Me-PEG) and evaluate their brain pharmacokinetics after administered nasally in rats. Methods NT-Ⅰ-NP was prepared by emulsion/solvent evaporation method and MePEG-PLA was used as the carrier material. Microdialysis technique and fluorospectrophotometry were used to determine NT-Ⅰ concentration after nasal administration in the brain of rats. Results The appearance of all NT-Ⅰ-NP groups was round or similar. The AUC(0-t) of below 100 nm NT-Ⅰ-NP was 1.22 fold as that of 100~200 nm NT-Ⅰ-NP,1.34 fold as that of 200~300 nm and 1.60 fold as that of exceed 300 nm NT-Ⅰ-NP(P