發(fā)布時(shí)間：2018-12-27 20:55

【摘要】：目的考察復(fù)方石杉?jí)A甲固體脂質(zhì)納米粒(HA-GB-SLN)在Beagle犬體內(nèi)藥動(dòng)學(xué)行為,并與市售石杉?jí)A甲片進(jìn)行比較。方法采用液相色譜-質(zhì)譜聯(lián)用法,以地西泮為石杉?jí)A甲的內(nèi)標(biāo),格列本脲為銀杏內(nèi)酯B的內(nèi)標(biāo),血漿樣品液-液提取后經(jīng)Diamonsil-C18(2.1 mm×150 mm,5μm)柱分離,流動(dòng)相:乙腈-甲醇-10 mmol·L-1乙酸銨(30∶40∶30,v/v/v,甲酸調(diào)p H 6~7),柱溫:25℃;流速:0.3 m L·min-1。石杉?jí)A甲采用正離子模式、銀杏內(nèi)酯B采用負(fù)離子模式,均采用多反應(yīng)監(jiān)測(cè)(MRM)方式進(jìn)行定量分析,監(jiān)測(cè)離子分別為m/z 243.2→210.2(石杉?jí)A甲)、m/z 285.2→193.2(地西泮)、m/z 423.1→367.3(銀杏內(nèi)酯B)和m/z 492.3→369.1(格列本脲),測(cè)定Beagle犬分別灌胃給予HA-GB-SLN和石杉?jí)A甲片后不同時(shí)間血漿中石杉?jí)A甲的濃度,通過DAS2.0藥動(dòng)學(xué)軟件計(jì)算藥動(dòng)學(xué)參數(shù),通過SPSS19.0統(tǒng)計(jì)軟件進(jìn)行參數(shù)的比較。結(jié)果 HA-GB-SLN與石杉?jí)A甲片的t1/2分別為(4.59±1.04)和(12.02±0.98)h,ρmax分別為(5.55±0.97)和(2.04±0.23)ng·m L-1,tmax分別為(2.92±0.37)和(8.33±0.82)h,MPT分別為(5.31±0.35)和(16.13±1.18)h。相對(duì)生物利用度為(157.67±4.85)%。銀杏內(nèi)酯B的t1/2為(2.81±0.35)h,ρmax為(45.91±2.89)ng·m L-1,tmax為(1.58±0.02)h,MRT為(6.96±0.33)h,AUC0-18為(510.79±17.77)ng·h·m L-1,AUC0-∞為(525.45±16.68)ng·h·m L-1。結(jié)論該法靈敏、簡(jiǎn)便、特異性強(qiáng)、可以用于定量生物樣品中的石杉?jí)A甲和銀杏內(nèi)酯B的濃度;并且與石杉?jí)A甲片比較,自制復(fù)方石杉?jí)A甲固體脂質(zhì)納米粒吸收好,起效快,生物利用度顯著提高。
[Abstract]:Objective to investigate the pharmacokinetic behavior of compound Huperzine A solid lipid nanoparticles (HA-GB-SLN) in Beagle dogs and compare it with Huperzine A tablets on the market. Methods using diazepam as the internal standard of Huperzine A and glibenclamide as the internal standard of ginkgolide B, the plasma samples were extracted by liquid-liquid extraction and separated by Diamonsil-C18 (2. 1 mm 脳 150 mm,5 渭 m) column. The mobile phase consisted of acetonitrile-methanol-10 mmol L-1 ammonium acetate (30: 40: 30v / v / v), and the column temperature was 25 鈩，

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