Zi-Min Yuan, Yue Chen, Hui Gao, Jia Lv, Gui-Rong Chen, Wang Jing
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
Pharmacogn Mag. 2017 Jan-Mar;13(49):51-57. doi: 10.4103/0973-1296.197632.
The Bile-processed (BRC), which has a colder drug property than (RC), is widely used for the treatment of heat syndrome. We compared the pharmacokinetics of the protoberberine-type alkaloids in BRC and RC in rats with heat syndrome to elucidate the bile-processing mechanism.
We established a rapid and sensitive method for simultaneously determining three alkaloids: berberine, palmatine, and jatrorrhizine, in rat plasma based on ultra-performance liquid chromatography/tandem mass spectrometry. The separation was carried out on a Waters ACQUITY BEA C column. The mobile phase consisted of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid and 10 mmol/L ammonium acetate) and carbamazepine was used as an internal standard. The detection was carried out in a multiple reaction monitoring mode (MRM) using electrospray ionization in the positive ion mode.
Pharmacokinetic profiles indicated that the C of berberine and palmatine increased two times and the T of the three alkaloids decreased three times after bile processing. AUC and AUC of the alkaloids were similar between RC and BRC.
The results suggest that bile processing could increase the absorption rate of alkaloids. This study broadens our understanding of Chinese herbal medicine processing.
Contents of berberine, palmatine and jatrorrhizine, in heat syndrome rats' plasma between the raw and bile-processed (RC) were determined by UPLC-MS/MS.The whole pharmacokinetic profiles of three alkaloids in the bile-processed (BRC) were similar to those of RC.The shorter T and increased 2-fold C were obtained after RC bile-processing.Bile-processing could promote the absorption rate of alkaloids in a certain degree. RC: , BRC: Bile-processed , HPLC: high-performance liquid chromatography, UPLC-MS/MS: ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry, LC-MS: liquid chromatography-mass spectrometry, MRM: multiple reaction monitoring mode, QC: quality control, RE: relative error, RSD: relative standard deviation, C: maxium of drug concentration, T: time for maxium of drug concentration, AUC: area under concentration-time curve, LLOQ: Linearity and lower limits of quantification, t: half-life, Clz: body clearance.
胆汁制（BRC）药性较生品（RC）寒凉，广泛用于治疗热证。我们比较了热证大鼠中BRC和RC中原小檗碱型生物碱的药代动力学，以阐明胆汁炮制机制。
我们基于超高效液相色谱/串联质谱建立了一种快速灵敏的方法，用于同时测定大鼠血浆中的三种生物碱：小檗碱、巴马汀和药根碱。分离在Waters ACQUITY BEA C柱上进行。流动相由乙腈（含0.1%甲酸）和水（含0.1%甲酸和10 mmol/L乙酸铵）组成，卡马西平用作内标。检测采用正离子模式下的电喷雾电离，在多反应监测模式（MRM）下进行。
药代动力学曲线表明，胆汁炮制后小檗碱和巴马汀的Cmax增加了两倍，三种生物碱的Tmax降低了三倍。RC和BRC中生物碱的AUC和AUC(0-t)相似。
结果表明胆汁炮制可提高生物碱的吸收速率。本研究拓宽了我们对中药炮制的理解。
采用UPLC-MS/MS法测定了热证大鼠血浆中生品与胆汁制（RC）中小檗碱、巴马汀和药根碱的含量。胆汁制（BRC）中三种生物碱的整体药代动力学曲线与RC相似。RC胆汁炮制后Tmax缩短，Cmax增加2倍。胆汁炮制在一定程度上可促进生物碱的吸收速率。RC：生品，BRC：胆汁制品，HPLC：高效液相色谱，UPLC-MS/MS：超高效液相色谱-质谱/质谱，LC-MS：液相色谱-质谱，MRM：多反应监测模式，QC：质量控制，RE：相对误差，RSD：相对标准偏差，Cmax：药物浓度最大值，Tmax：药物浓度达最大值的时间，AUC：浓度-时间曲线下面积，LLOQ：线性和定量下限，t1/2：半衰期，Clz：机体清除率
