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 the 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 quanti?cation 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 quanti?cation 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, signi?cant 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 signi?cantly higher than those in normal rats. Besides, the protoberberine-type alkaloids could bring a direct effect on the neuron in the hippocampus.
关键词:
脑内药动学;失眠大鼠;交泰丸;LC-MS/MS;微透析;原小檗碱型生物碱
Keywords:
Project Supported:
This work was supported by the National Natural Science Foundation of China (No. 81473319 and No. 81473540), the Key Projects of Guangdong Natural Science Foundation (No. 2017A030311022), the Guangdong Science and Technology Program (No. 2015A030401031, 2014A020209026), the Guangdong Natural Science Foundation (No. 2015A030313123), the Zhongshan Science and Technology Program (No. 2016C1015), and the Science Program for Overseas Scholar of Guangzhou University of Chinese Medicine (Torch Program) (No. XH20170111).
Xiao-jun Zhang, Jia-hui Chen, Liang Luo, Wei He, Guang-hui Liu, Jing Gong, Yi-feng Zeng, Zhi-yong Xie, Qiong-feng Liao*. Comparative Brain Pharmacokinetic Study of Jiaotai Pills in Normal and Insomnic Rats using Brain Microdialysis Combinated with LC-MS/MS[J]. Chinese Herbal Medicines (CHM),2018,10(2):205-213
