复方石杉碱甲固体脂质纳米粒Beagle犬体内药动学

发布时间：2018-12-27 20:55

【摘要】：目的考察复方石杉碱甲固体脂质纳米粒(HA-GB-SLN)在Beagle犬体内药动学行为,并与市售石杉碱甲片进行比较。方法采用液相色谱-质谱联用法,以地西泮为石杉碱甲的内标,格列本脲为银杏内酯B的内标,血浆样品液-液提取后经Diamonsil-C18(2.1 mm×150 mm,5μm)柱分离,流动相:乙腈-甲醇-10 mmol·L-1乙酸铵(30∶40∶30,v/v/v,甲酸调p H 6~7),柱温:25℃;流速:0.3 m L·min-1。石杉碱甲采用正离子模式、银杏内酯B采用负离子模式,均采用多反应监测(MRM)方式进行定量分析,监测离子分别为m/z 243.2→210.2(石杉碱甲)、m/z 285.2→193.2(地西泮)、m/z 423.1→367.3(银杏内酯B)和m/z 492.3→369.1(格列本脲),测定Beagle犬分别灌胃给予HA-GB-SLN和石杉碱甲片后不同时间血浆中石杉碱甲的浓度,通过DAS2.0药动学软件计算药动学参数,通过SPSS19.0统计软件进行参数的比较。结果 HA-GB-SLN与石杉碱甲片的t1/2分别为(4.59±1.04)和(12.02±0.98)h,ρmax分别为(5.55±0.97)和(2.04±0.23)ng·m L-1,tmax分别为(2.92±0.37)和(8.33±0.82)h,MPT分别为(5.31±0.35)和(16.13±1.18)h。相对生物利用度为(157.67±4.85)%。银杏内酯B的t1/2为(2.81±0.35)h,ρmax为(45.91±2.89)ng·m L-1,tmax为(1.58±0.02)h,MRT为(6.96±0.33)h,AUC0-18为(510.79±17.77)ng·h·m L-1,AUC0-∞为(525.45±16.68)ng·h·m L-1。结论该法灵敏、简便、特异性强、可以用于定量生物样品中的石杉碱甲和银杏内酯B的浓度;并且与石杉碱甲片比较,自制复方石杉碱甲固体脂质纳米粒吸收好,起效快,生物利用度显著提高。
[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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