000001a2李晓宇-应用的药理.doc

荷叶碱大鼠研究(李晓宇1，周尔君2，顾圣莹1，徐媛1，刘皋林1（1.上海交通大学附属第一人民医院药剂科，上海，200080；2. 上海交通大学附属胸科医院药剂科，上海，200030） 摘要： 目的 用肠管外翻模型研究荷叶碱在大鼠不同肠段的体外肠吸收特征。方法 在不同肠段(十二指肠、空肠、回肠和结肠)的肠管外翻模型中分别加入10μg·mL -1 、20μg·mL -1和40μg·mL -1的荷叶碱，在不同时间点取样，采用Agilent 1100型高效液相色谱仪测定肠囊内药物浓度，优化的色谱条件如下：Agilent 1100色谱工作站，Sinochrom ODS-BP色谱柱（5μm，250mm×4.6mm）；流动相：乙腈-水-冰醋酸-三乙胺（40：60：0.5：0.43）；流速：1.1mL/min；柱温：30℃；进样量：20μL；紫外检测波长：272nm。计算荷叶碱的吸收参数来分析其在肠道的吸收特征，比较不同肠段对荷叶碱通透能力的差异。结果 37℃下，不同浓度的荷叶碱在台氏液中2.5h内稳定，方法学考察均符合生物样品的测定要求。荷叶碱在大鼠不同肠段中的吸收在一定浓度内无饱和现象，十二指肠、空肠、回肠和结肠的吸收速率常数依次为0.0144±0.0054、0.0196±0.0033、0.0215±0.0044、0.0178±0.0032 min-1。结论 荷叶碱在大鼠不同肠段的转运为一被动扩散过程，不同肠段的吸收具有线性特征，吸收速度依次如下：回肠、空肠、结肠和十二指肠。 荷叶碱，肠管外翻模型，高效液相色谱，吸收Absorption profiles studies of Nuciferine in rats intestine LI Xiao-yu1, ZHOU Er-jun2, GU Sheng-ying1, XU Yuan1, LIU Gao-lin1 (1. First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080;2. Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030 ABSTRACT: OBJECTIVE To study the absorption profiles of nuciferine at the different intestinal section (duodenum, jejunum, ileum and colon). METHODS Sac containing drug free Tyrode solution was immersed into the Tyrode solution which containing 10, 20 and 40 μg·mL-1 nuciferine. The solution inside the sac was collected and drug concentration was determined by HPLC method. Optimized chromatographic condition displayed as follow: Sinochrom ODS-BP (5μm, 4.6mm×250 mm) column was used for the separation of nuciferine with acetomitrile-water-acetic acid-TEA (40:60;0.5:0.43) as mobile phase. Nuciferine was detected at wavelength of 272 nm. Flow rate was 1.1 mL/min. The column temperature was 30℃. Absorption parameter of nuciferine in different part of rat intestine was obtained to evaluate its profiles. RESULTS Different concentration of Nuciferine was stable in tyrode solution in 37℃ within 2.5 h. Developed method was validated for the determination of nuciferine in tyrode solution. The absorption of nuciferine in different