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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。
OBJECTIVE To investigate the pharmacokinetics of compound huperzine A solid lipid nanoparticles (HA-GB-SLN) in Beagle dogs and to compare with huperzine tablets. Methods The internal standard of huperzine A was obtained by liquid chromatography-mass spectrometry (GC-MS). Glibenclamide was the internal standard of Ginkgolide B. The plasma samples were digested with Diamonsil-C18 (2.1 mm × 150 mm, 5 μm). The mobile phase was acetonitrile-methanol-10 mmol·L-1 ammonium acetate (30:40:30, v / v / ℃; flow rate: 0.3 m L · min-1. Huperzine A was in positive mode, while Ginkgolide B was in negative ion mode. Quantitative analysis was carried out by multi-reaction monitoring (MRM). The monitored ions were m / z 243.2 → 210.2 (huperzine A), m / z Beagle dogs were orally administrated with HA-GB-SLN and Huperzhanil, respectively, from 285.2 → 193.2 (diazepam), m / z 423.1 → 367.3 (ginkgolide B) and m / z 492.3 → 369.1 (glibenclamide) The plasma concentration of huperzine A at different times after the administration of caffeine, the pharmacokinetic parameters were calculated by DAS2.0 pharmacokinetic software, and the parameters were compared by SPSS19.0 statistical software. Results The t1 / 2 of HA-GB-SLN and huperzine tablets were (4.59 ± 1.04) and (12.02 ± 0.98) h, respectively, and the values of ρmax were (5.55 ± 0.97) and (2.04 ± 0.23) ng · m L- 1 and tmax were (2.92 ± 0.37) and (8.33 ± 0.82) h respectively, MPT was (5.31 ± 0.35) and (16.13 ± 1.18) h, respectively. The relative bioavailability was (157.67 ± 4.85)%. The results showed that ginkgolide B had a significant reduction in t 1/2 of (2.81 ± 0.35) h, pmax of (45.91 ± 2.89) ng · m L -1, tmax of (1.58 ± 0.02) h and MRT of (6.96 ± 0.33) 18 was 510.79 ± 17.77 ng · h · m L-1, and AUC0-∞ was (525.45 ± 16.68) ng · h · m L-1. Conclusion The method is sensitive, simple and specific, and can be used to quantify the concentration of huperzine A and ginkgolide B in biological samples. Compared with huperzine A tablet, self-made huperzine A solid lipid nano Granules absorbed well, rapid onset, bioavailability significantly increased.