Tsai Tung-Hu, Liu Mei-Chun
National Research Institute of Chinese Medicine, 155-1, Li-Nong Street Section 2, Shih-Pai, Taipei 112, Taiwan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jul 5;806(2):161-6. doi: 10.1016/j.jchromb.2004.03.047.
A method coupled with microdialysis technique and liquid chromatography was applied in the continuous and concurrent in vivo monitoring of extracellular hesperidin in the blood and bile of anaesthetized rats. Hesperidin was intravenously administered via the femoral vein. Sampling was achieved using two microdialysis probes, which were implanted into the jugular vein and into the bile duct. Dialysates of blood and bile were both directly injected onto the liquid chromatographic system, so no further clean-up procedures were required. Separation was performed using a reversed phase ODS-2 microbore column 150 mm x 1 mm i.d., particle size 5 microm with mobile phase of acetonitrile-0.1M ammonium acetate (30:70, v/v) at flow-rate of 0.05 ml/min. The UV detection for hesperidin was set at a wavelength of 283 nm. This method was used to determine the pharmacokinetics of hesperidin and its interaction in the presence of cyclosporin A, which is a P-glycoprotein modulator. The results indicate that the curve of area under the concentration versus time (AUC) for hesperidin in bile was significantly greater than that for hesperidin in blood at the dose of 30 mg/kg. The blood-to-bile distribution ratio (k = AUC(bile)/AUC(blood)) was 8.9 +/- 2.5 for hesperidin at 30 mg/kg. Following cyclosporin A treatment, the distribution ratio was reduced to 3.2 +/- 0.6. In conclusion, hesperidin goes through hepatobiliary elimination against the concentration gradient from blood to bile, and this hepatobiliary excretion of hesperidin may be regulated by the P-glycoprotein.
一种结合微透析技术和液相色谱的方法被用于在麻醉大鼠的血液和胆汁中连续同步地体内监测细胞外橙皮苷。橙皮苷通过股静脉静脉注射给药。使用两个微透析探针进行采样，这两个探针分别植入颈静脉和胆管。血液和胆汁的透析液都直接注入液相色谱系统，因此无需进一步的净化程序。使用反相ODS - 2微径柱（150 mm×1 mm内径，粒径5微米）进行分离，流动相为乙腈 - 0.1M醋酸铵（30:70，v/v），流速为0.05 ml/min。橙皮苷的紫外检测波长设定为283 nm。该方法用于测定橙皮苷的药代动力学及其在存在P - 糖蛋白调节剂环孢素A时的相互作用。结果表明，在30 mg/kg剂量下，胆汁中橙皮苷的浓度 - 时间曲线下面积（AUC）显著大于血液中橙皮苷的AUC。30 mg/kg橙皮苷的血 - 胆汁分布比（k = AUC（胆汁）/AUC（血液））为8.9±2.5。环孢素A处理后，分布比降至3.2±0.6。总之，橙皮苷通过肝胆消除，从血液到胆汁呈浓度梯度，并且橙皮苷的这种肝胆排泄可能受P - 糖蛋白调节。
