黄芩苷及三七总皂苷配伍脑脊液药代动力学研究

Pharmacokinetic studies of baicalin and compatibility of baicalin-Panax Notoginsenosides in rat cerebrospinal fluid

目的建立大鼠脑脊液中黄芩苷的HPLC-MS/MS测定方法,研究黄芩苷及配伍三七总皂苷的大鼠脑脊液药代动力学变化。方法大鼠尾静脉注射黄芩苷和黄芩苷-三七总皂苷配伍溶液,采集脑脊液样品,利用LC-MS/MS测定脑脊液中黄芩苷的含量。色谱柱为Agilent Eclipse XDB-C18(4.6 mm×150 mm,5μm),流动相为乙腈:1 mmol·L-1乙酸铵(含0.1%甲酸):0.1%氨水梯度洗脱;质谱检测离子为m/z 445/269(黄芩苷[M-1]-),m/z 237/194(卡马西平[M+1]+)。结果在5～200μg·L-1范围内,黄芩苷与内标卡马西平的峰面积比值与浓度的线性关系良好,回收率为87.15%～92.73%。黄芩苷在单独给药组和三七总皂苷配伍组的药代动力学参数分别为:Cmax为(189.67±20.13)、(237.00±51.86)μg·L-1,AUC0-t为(6612.96±1023.65)、(5466.63±267.06)μg·min·L-1,AUC0-∞为(6930.43±1060.41)、(5682.13±412.79)μg·min·L-1,T12为(108.84±45.67)、(102.54±38.37)min,CL为(15.39±2.60)、(18.32±0.88)L·min-1·kg-1。结论建立的HPLC-MS/MS测定方法能够准确灵敏地测定脑脊液中的黄芩苷。黄芩苷能够透过血脑屏障进入大鼠脑脊液,合用三七总皂苷后黄芩苷的药代动力学参数无明显变化,说明三七总皂苷对黄芩苷的脑脊液代谢没有明显影响。

Aim To establish a HPLC-MS-MS method for the determination of baicalin in rat cerebrospinal fluid（CSF） and investigate the pharmacokinetics of baicalin and compatibility with Panax Notoginsenosides（PNS）.Methods After baicalin and compatibility of BA-PNS were given by intravenous administration,the concentration of baicalin in rat CSF was determined by HPLC-MS-MS.Chromatographic separation was performed on an Agilent Eclipse XDB-C18（4.6 mm×150 mm,5 μm） within 7 min,with the mobile gradientphase of acetonitrile：1mmol·L-1 ammonium acetate（containing 0.1% formic acid）： 0.1% ammonia.The target ion transitions were m/z 445/269（baicalin-） and m/z 237/194（Carbamazepine ＋）.Results Calibration curves were linear over the concentration range from 5~200 μg·L-1for baicalin,with the recovery rates between 87.15%~92.73%.The pharmacokinetic parameters after a single dose of baicalin and baicalin-PNS were as follows： Cmax：（189.67±20.13）,（237.00±51.86） μg·L-1;AUC0-t：（6612.96 ±1023.65）,（5466.63±267.06） μg·min·L-1;AUC0-∞（6930.43±1060.41）,（5682.13±412.79） μg·min·L-1;T1[]2：（108.84±45.67）,（102.54±38.37） min;CL：（15.39±2.60）,（18.32±0.88） L·min-1·kg-1.Conclusion The method is proved to be accurate and convenient to determine baicalin in rat cerebrospinal fluid.Baicalin can pass through blood-brain barrier and enter the cerebrospinal fluid.The pharmacokinetic parameters of baicalin have not changed,so PNS has no effect on the CSF pharmacokinetic of baicalin.