牛蒡苷元纳米乳在大鼠体内的药动学研究

Pharmacokinetics of Arctigenin Nanoemulsion in Rats

目的建立测定牛蒡苷元在大鼠血浆中药物浓度的高效液相色谱法，研究牛蒡苷元纳米乳在大鼠体内的药动学特征。方法血浆样品经乙酸乙酯萃取处理，色谱柱为AgilentC18柱（4．6mm×250mm，5μm），流动相为甲醇-0．2％磷酸水（52：48，V／V），检测波长为280nm，以槲皮素为内标。以4mg·kg^-1的剂量给大鼠iv牛蒡苷元纳米乳，测定不同时间点的血药浓度，用DAS2．1软件计算药动学参数。结果牛蒡苷元在0．1～10mg·L^-1内线性关系良好（r=0．9992），定量下限为0．1mg·L^-1，最低检测限为0．03mg·L^-1,提取回收率在85％以上，日内、日间RSD均小于6％。牛蒡苷元在大鼠体内的过程符合二室模型，分布半衰期和消除半衰期分别为（0．134±0．085）、（1．471±0．164）h。结论本方法可用于测定牛蒡苷元在大鼠血浆中的药物浓度，牛蒡苷元纳米乳在大鼠体内迅速分布，而且消除较慢。

OBJECTIVE To develop an HPLC method for the determination of arctigenin in rat plasma and study the pharmacoki-netics of arctigenin nanoemulsion. METHODS The plasma samples were extracted by ethyl acetate. The determination was carried out on an Agilent C18 column （ 4.6mm×250mm,5μm） with the mobile phase consisting of methanol-0. 2% phosphoric acid （52： 48, V/V） and the UV detection wavelength was set at 280 nm. Quereetin was selected as internal standard. Arctigenin nanoemulsion was administered to rats by intravenous injection at a dose of 4 mg · kg^-1. The plasma concentration of arctigenin at different time points was determined by the established HPLC method. The pharmacokinetic parameters were processed by DAS2. 1 software. RE-SULTS The calibration curve of arctigenin had acceptable linearity in the range of 0. 1 - 10 mg· L^-1 in rat plasma（ r = 0. 999 2）. The lower limit of quantitation （LLOQ） was estimated to be 0. 1 mg · L^ - 1 and the lower limit of detection （LLOD） was estimated to be 0. 03 mg · L^ - 1. The mean extraction recovery rates of arctigenin QC samples at low, medium and high concentration levels were all a-bove 85%. The intra-day and inter-day precisions were less than 6%. The pharmacokinetics of arctigenin in rats after intravenous in-jection were fitted to a two-compartment mode] and the half-lives of ct phase and β phase were （0. 134 ± 0. 085 ） and （ 1. 471 ± 0. 164） h, respectively. CONCLUSION The HPLC method is simple, rapid and accurate. It can be used for monitoring the plasma concen- tration of arctigenin and its pharmacokinetic study. After intravenous administration of arctigenin nanoemulsion, arctigenin is rapidly distributed into tissues, but the elimination is slow.