摘要
目的：研究胡黄连苷Ⅱ在大鼠体内的药代动力学。方法：大鼠单剂量静注给予胡黄连苷Ⅱ后，采用HPLC-MS法测定大鼠血浆、组织、粪便、尿液及胆汁中的胡黄连苷Ⅱ。色谱柱为Hypersil ODS2柱，（5μm，150mm×4．6mm），流动相为甲醇：水（47：53），内标为替硝唑。ESI选择正离子检测：检测离子为[M＋Na]^＋m/z535．00（胡黄连苷Ⅱ）、[M＋H]^＋m／z247．90（内标）。结果：血浆样品中，胡黄连苷Ⅱ的线性范围为0．05．20．0μg·mL^-1（r=0.9998）；各浓度的提取回收率均大于76％；最低定量限为0．05μg·mL^-1。静注给予2.5、5.0、10.0mg·kg^-1后，大鼠体内胡黄连苷Ⅱ浓度快速降低，平均消除半衰期仅为19．6min。AUC与剂量呈现良好的线性相关性，提示胡黄连苷Ⅱ在大鼠体内的处置属于线性动力学。静脉注射给药后胡黄连苷Ⅱ广泛分布于各组织，其中肾和肝组织中浓度最高。胡黄连苷Ⅱ主要通过尿液和胆汁排泄，在尿液中的平均累积排泄百分率为11．79％；胆汁中平均累积排泄百分率为7．80％；粪便中未检测出胡黄连苷Ⅱ。胡黄连苷Ⅱ平均血浆蛋白结合率为30．0％。结论：静注给药后，胡黄连苷Ⅱ迅速从大鼠体内消除，并可在体内广泛分布。有约19．59％以原型形式从胆汁和尿液排泄。
AIM： To study the pharmacokinetics of picroside Ⅱ in rats. METHODS： Following iv. administration to rats, HPLC-MS was used to determine picroside Ⅱ concentration in plasma, tissues, feces, urine and bile. A Hypersil ODS2 column （5 μm, 150 mm×4.6 mm I.D.） was used with a mobile phase consisting of methanol-water （47：53, v/v）. The protonized canions [M＋Na]^＋ at m/z 535.00 of picroside Ⅱ, and [M＋H]^＋at m/z 247.90 of tinidazole （IS） were analyzed by LC-ESI-MS in selected ion monitoring （SIM） mode. RESULTS： The linear range of picroside Ⅱ in plasma was 0.05-20.0 μg·mL-1 and the limit of quantitation of picroside II was 0.05 μg·mL^-1 with a recovery of more than 76%. After iv. administration of 2.5, 5.0 and 10.0 mg·kg^-1, the concentration of picroside II in rats declined rapidly with mean elimination half-life time （t1/2β） of about 19.6 min. The relationship between dose and AUC showed linearity, suggesting that there was linear disposition of picroside Ⅱ in rats in the dose range. Following iv. administration to rats, picroside II was mainly distributed in kidney and liver. Picroside Ⅱ was mainly excreted through bile and urine. 11.79% and 7.80% of the given dose were separately excreted in urine and bile. No picroside Ⅱ was detected in the feces. Moreover, the mean plasma protein bounding ratio of picroside Ⅱ was 30.0%. CONCLUSION： Picroside Ⅱ can be rapidly eliminated from the rat plasma, extensively distributed and 19.59% of the given dose is mainly excreted in the bile and urine in parent form after iv. administration.
出处
《中国天然药物》
SCIE
CAS
CSCD
2008年第5期382-386,共5页
基金
国家自然科学基金资助项目(30472060)~~
