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Analytical Methods · 2014 ·Vol. 6 ·期 9 ·2998-3008 · IF 1.938

The simultaneous determination of berberine, palmatine, coptisine, epiberberine and jatrorrhizine in rat plasma by LC-MS/MS and a pharmacokinetic comparison after the oral administration of Rhizoma coptidis and Jiao-Tai-Wan extract

Guanghui Liu,Wei He,Hao Cai,Xiuman Sun,Waner Hou,Manna Lin,Zhiyong Xie,Qiongfeng Liao

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine berberine, palmatine, coptisine, epiberberine and jatrorrhizine in rat plasma, using tetrahydropalmatine as an internal standard. The separation of the five compounds was carried out on a C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0 with formic acid). The detection was performed in the multiple reaction monitoring (MRM) mode via the electrospray ionization (ESI) source operating in the positive ionization mode. Linear calibration curves were obtained over the concentration range of 0.20–200.0 ng ml−1 for berberine, and 0.20–100.0 ng ml−1 for palmatine, coptisine, epiberberine and jatrorrhizine. The accuracy, precision and extraction recovery of the five analytes were all satisfactory. The validated method was successfully applied to study the pharmacokinetic differences of the five protoberberine-type alkaloids after the oral administration of Rhizoma coptidis (RC) and Jiao-Tai-Wan (JTW) extract. It was found that the Tmax values of the five ingredients in the JTW extract were significantly increased (P < 0.05) when compared with those in RC. In addition, the AUC0–t of palmatine, coptisine and epiberberine were significantly increased (P < 0.05).

CAS / MDL: 631-61-8
研究领域: 药理学 · 分析化学 · 中医药学
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Chinese Herbal Medicines · 2018 · IF 0

Comparative brain pharmacokinetic study of Jiaotai pills in normal and insomnic rats using brain microdialysis combinated with LC–MS/MS

Xiao-jun Zhang,Jia-hui Chen,Liang Luo,Wei He,Guang-hui Liu,Jing Gong,Yi-feng Zeng,Zhi-yong Xie,Qiong-feng Liao

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 C 18 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 T 1/2 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.

CAS / MDL: 631-61-8
研究领域: 药理学 · 神经科学 · 分析化学
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JOURNAL OF ETHNOPHARMACOLOGY · 2014 · IF 2.939

Integrated pharmacokinetics of five protoberberine-type alkaloids in normal and insomnic rats after single and multiple oral administration of Jiao-Tai-Wan

Wei He,Guanghui Liu,Hao Cai,Xiuman Sun,Waner Hou,Peiting Zhang,Zhiyong Xie,Qiongfeng Liao

Ethnopharmacological relevance Jiao-Tai-Wan (JTW), an important herbal formula consists of Rhizoma coptidis and Cortex cinnamomi powder, is a famous prescription which has been used for centuries to treat insomnia in Traditional Chinese Medicine . The purpose of this study is to compare the pharmacokinetic properties of five protoberberine-type alkaloids (i.e. berberine , palmatine , coptisine , epiberberine and jatrorrhizine), the main bioactive constituents in JTW, between normal and insomnic rats. We also investigate the differences between single-dose and multiple-dose pharmacokinetics of five protoberberine-type alkaloids. Materials and methods The insomnic rat models were induced by intraperitoneal injection of one-dose para-chlorophenylalanine acid (PCPA). Quantification of five protoberberine-type alkaloids in rat plasma was achieved by using a rapid LC–MS/MS method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time and estimate pharmacokinetic parameters . An unpaired Student׳s t test was used for comparisons with SPSS 17.0. Results The five protoberberine-type alkaloids of single-dose normal groups had slow absorption and low bioavailability, as well as a delay of peak time. In the single-dose oral administration, the C max and T max of five ingredients in insomnic rats had significant differences compared with those of normal rats. In the multiple-dose oral administration, the pharmacokinetic parameters of five protoberberine-type alkaloids varied greatly in insomnic rats. In the normal rats, there were significant differences ( P <0.05) in the principal pharmacokinetic parameters such as C max and T max between single-dose and multiple-dose oral administration. In the insomnic rats, the five ingredients of multiple-dose groups showed better absorption than the single-dose groups. Particularly, three peaks were observed in multiple-dose model group of plasma–concentration curves. Conclusions The pharmacokinetic behavior of five protoberberine-type alkaloids was described in this paper. In both normal groups and model groups, the pharmacokinetic behavior of multiple-dose had significant differences comparing with the single-dose; either single-dose or multiple-dose, the pharmacokinetic behavior of insomnic rats had significant differences comparing the normal rats. Multiple dosing may improve the absorption of JTW in insomnic rats, which will increase the bioavailability and bring into active role in therapeutical effect.

CAS / MDL: 631-61-8
研究领域: 药理学 · 中医药学 · 民族药理学
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