UPLC-MS/MS分析瓜蒌子中3,29-二苯甲酰基栝楼仁三醇在大鼠体内的组织分布情况  

Tissue Distribution of 3,29-Dibenzoyl Rarounitriol from Trichosanthis Semen in Rats by UPLC-MS/MS

作　　者：冯果[1,2] 吴增光 何新 李玮[1] 李横[4] 郑传奇 刘青[1] 陈荧荧[1] 

机构地区：[1]贵阳中医学院,贵阳550025 [2]国家苗药工程技术研究中心,贵阳550025 [3]天津中医药大学,天津300193 [4]贵州仁德绿色产业开发有限公司,贵阳550001

出　　处：《中国实验方剂学杂志》2017年第21期86-92,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：贵州省中药现代化科技产业研究开发专项(黔科合中药字[2013]5049号);贵州省教育厅产学研基地项目(黔教合KY字[2013]123号);国家中医药管理局中医药部门公共卫生服务项目([2015]136);贵州省高校工程技术研究中心建设项目(黔教合KY字[2012]021号)

摘　　要：目的:探讨瓜蒌子的有效成分3,29-二苯甲酰基栝楼仁三醇口服给药后在大鼠体内的组织分布情况。方法:取健康SD雄性大鼠,灌胃给药后分别于时间点0.5,1,3,6 h取大鼠的胃、心、肝、脾、肺、肾组织,将组织匀浆及预处理。采用ZORBAX C18色谱柱(2.1 mm×50 mm,3.5μm),流动相含0.1%甲酸的10 mmol·L^(-1)乙酸铵溶液(A)-甲醇(B)梯度洗脱(0~0.01 min,50%A;0.01~1.0 min,50%~2%A;1.0~4.0 min,2%A;4.0~4.1 min,2%~50%A;4.1~5.0 min,50%A),流速0.5 m L·min^(-1),进样量10μL,选择电喷雾离子化三重四极杆串联质谱,以多反应监测(MRM)方式进行正离子模式检测,用于定量分析二级碎片离子分别为m/z 684.7~527.6(3,29-二苯甲酰基栝楼仁三醇)和m/z 472.4~436.4(特非那定)。结果:大鼠灌胃给药3,29-二苯甲酰基栝楼仁三醇后,在肺组织中0.5 h时药物质量分数达峰值,在心、肝、脾、肾中1.0 h时药物质量分数达峰值,而胃中在3.0 h时药物质量分数达峰值。胃和肺中药物分布较大,在胃中3.0 h时药物质量分数达最大值(405.8±114.8)ng·g^(-1);药物在肺中的分布速度最快,0.5 h时即可达到峰值(338.8±85.5)ng·g^(-1),在心、肝、脾和肾脏的分布较低,6 h时各脏器的药物质量分数已显著降低。结论:大鼠灌胃给予3,29-二苯甲酰基栝楼仁三醇后,能分布到各脏器组织,其中在胃和肺分布的浓度较高,且在3 h后仍能保持较高水平,而在心、肝、脾、肾分布浓度相对较低,这可能与该成分本身性质和作用特点有关。Objective： To investigate the tissue distribution of 3, 29-dibenzoyl rarounitriol from Trichosanthis Semen in rats after oral administration. Method： The stomach, heart, liver, spleen, lung and kidney in heahhy male SD rats were taken at 0.5, 1, 3, 6 h after intragastric administration, tissue homogenates and pretreatment were performed. ZORBAX C18 column （2.1 mm ~ 50 mm, 3.5 μm） was adopted with mobile phase of 10 mmol-L-1 ammonium acetate （containing 0. 1% formic acid） -methanol for gradient elution, flow rate was 0. 5 mL·min-1, the injection volume of 10 μL. A triple quadrupole tandem mass spectrometry equipped with electrospray ionization source was used as detector and operated by multiple reaction monitoring （MRM） positive ion mode of the transitions m/z 684.7-527.6, m/z 472.4-436.4 for 3, 29-dibenzoyl rarounitriol and terfenadine, respectively. Result： After intragastrie administration of 3, 29-dibenzoyl rarounitriol in rats, peak concentration in the lung reached at 0.5 h, that in the heart, liver, spleen and kidney reached at 1.0 h, but that in the stomach at 3.0 h. The distribution of drug in the stomach and lung is large, its concentration in the stomach at 3.0 h was （405.8 ± 114.8） ng·g-1 ^-1; but the drug distributed fastest in the lung, it can reached a high concentration of （338.8 ± 85.5） ng·g-1 at 0.5 h, distribution of 3, 29-dibenzoyl rarounitriol in the heart, liver, spleen and kidney was low, the drug concentration in each organ were significantly reduced at 6.0 h. Conclusion ： After intragastrie administration of 3, 29-dibenzoyl rarounitriol, it can be distributed to each organ tissue, which has high concentration in the stomach and lung, and this drug can still maintain a high level after 3 h, but its concentrations in the heart, liver, spleen and kidney are relatively low, which may be related to the nature characteristics and the acting features of itself.

关 键 词：瓜蒌子 3 29-二苯甲酰基栝楼仁三醇 特非那定 组织分布 方法学 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]