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Agilent C₁₈柱(4.6 mm×250 mm, 5 μm),流动相为甲醇-0.2%磷酸水(52∶48,V/V),检测波长为280 nm,以槲皮素为内标。以4 mg·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0.1~10 mg·L^-1内线性关系良好(r=0.999 2),定量下限为0.1 mg·L^-1,最低检测限为0.03 mg·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 pharmacokinetics of arctigenin nanoemulsion. METHODS The plasma samples were extracted by ethyl acetate. The determination was carried out on an Agilent C₁₈ column (4.6 mm×250 mm, 5 μm) 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. Quercetin 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. RESULTS 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^-1and 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 above 85%. The intra-day and inter-day precisions were less than 6%. The pharmacokinetics of arctigenin in rats after intravenous injection were fitted to a two-compartment model and the half-lives of α 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 concentration of arctigenin and its pharmacokinetic study. After intravenous administration of arctigenin nanoemulsion, arctigenin is rapidly distributed into tissues,but the elimination is slow.