贵州医科大学学报

2018, v.43;No.214(07) 745-749

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白头翁皂苷B4在大鼠体内药代动力学规律及肺组织分布
Pharmacokinetics and Lung Tissue Distribution of Anemoside B4 in Rats

狄孟华;李桂凤;李言;崔京浩;王永林;杨世林;
DI Menghua;LI Guifeng;LI Yan;CUI Jinghao;WANG Yonglin;YANG Shilin;Guizhou Medical University;College of Pharmacy,Soochow University;

摘要(Abstract):

目的:建立用高效液相色谱(HPLC)法测定Wistar大鼠血浆及肺组织中白头翁皂苷B4(B4)的含量,研究其在大鼠体内的药代动力学规律及肺组织分布特征。方法:以气管滴注给予6 mg/kg的白头翁皂苷B4的大鼠作为气管滴注组,并与尾静脉给予6 mg/kg白头翁皂苷B4注射的大鼠作为尾静脉注射组,采用HPLC法于不同时间点(第5、15、30 min及1、2、4、6、8、10、12、14、24 h)的血药浓度,并于给药后5 min及1、2、4、8、12、24 h时测定测定气管滴注组大鼠肺组织中的B4浓度。结果:HPLC法测定血浆样品及肺组织样品中的内源性物质未对B4的检测结果形成干扰,B4在血浆及肺组织中的浓度分别在0.5~100.0 mg/L、0.5~400.0 mg/L范围与峰面积线性关系良好,最低定量限均为0.5 mg/L(S/N>10);室温下24 h的稳定性RE<11%,3次冻融稳定性RE<13%;白头翁皂苷B4在大鼠体内药动学过程符合二室模型;HPLC法测定结果表明,大鼠经气管滴注给药后,药物在肺中积蓄,且缓慢释放入血。结论:建立的HPLC法稳定可靠,肺部给予药物白头翁皂苷B4后,药物在肺中产生积蓄,缓慢入血,延长在体内的保留时间。
Objective: To establish a HPLC method to determine anemoside B4 content in rat plasma and lung tissue,and study pharmacokinetics and distribution in lung tissue in rats. Methods: B4( 6 mg/kg) was administered by intratracheal instillation and compared with the intravenous injection group with same quantity. Adopting HPLC method to determine plasma-drug concentration at different time point( at 5,15,30 min and 1,2,4,6,8,10,12,14,24 h); drug concentration was determined after intratracheal instillation of B4 in rat( at 5 min after drug and 1,2,4,8,12,24 h). Results: Endogenous substances in plasma sample and lung tissue samples did not interfere with the B4 test results;B4 showed good peak area linear relationship with the plasma and lung tissue with the concentration of0. 5 ~ 100. 0 mg/L and 0. 5 ~ 400. 0 mg/L,with low quantification limit of 0. 5 mg/L( S/N > 10);24 h under room temperature showed stability RE < 11%,three times freeze-thaw stability was RE <13%; the pharmacokinetics of B4 conformed to a two-compartment model after intratracheal instillation and intravenous injection. B4 was administered via tracheal instillation,drugs accumulated in the lungs and then slowly released to blood. Conclusions: Stable HPLC method was successfully developed. B4 was administered via tracheal instillation,drugs accumulate in the lungs,slowly enter the blood and prolong the retention time in the body.

关键词(KeyWords): 药代动力学;高效液相色谱;白头翁皂苷B4;气管滴注;肺组织;血浆
pharmacokinetics;high efficiency liquid chromatography;anemoside B4;tracheal drip;lung tissue;plasma

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基金项目(Foundation): 国家自然科学基金项目资助(K113231513)

作者(Author): 狄孟华;李桂凤;李言;崔京浩;王永林;杨世林;
DI Menghua;LI Guifeng;LI Yan;CUI Jinghao;WANG Yonglin;YANG Shilin;Guizhou Medical University;College of Pharmacy,Soochow University;

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