目的:采用微透析技术结合液相色谱质-谱联用法(LC-MSM/S)研究金刚烷胺在大鼠纹状体细胞外液中的药代动力学(药动学)过程,探讨靶器官药动学研究方法.方法:SD大鼠(雄性,8~10周龄)行乌拉坦麻醉(1.0 g/kg)后,手术植入微透析探针于大鼠纹状体,以人工脑脊液恒速(2μL/min)灌注探针.灌注1 h后,腹腔注射盐酸金刚烷胺(1.0 mg/kg),注射后立即收集透析液样本,样本收集间隔时间为12 min,连续6 h.用LC-MS/MS法检测透析样本中金刚烷胺浓度,药物浓度-时间曲线及计算药动学参数用DAS软件拟合.结果:金刚烷胺在大鼠纹状体细胞外液中浓度-时间变化呈一室开放模型,其主要药动学参数Tmax、Cmax、t1/2和AUC 0-∞为(1.78±0.59)h、(38.56±91.0)μgL/、(2.07±0.35)h和(5918.4±278.39)μg/(L·h).结论:本实验建立了一种基于微透析采样结合LC-MS/MS法研究金刚烷胺在大鼠纹状体细胞外液中药代动力学过程的实验方法,该方法操作简单、灵敏度高,为研究药物在靶器官中的药动学过程提供了方法学基础.%Objective:To explore the research method for pharmacokinetics of drugs in target organs via examining the pharmacokinetic process of amanta-dine in the extracellular fluid of striatum of rats using in vivo microdialysis and liquid chromatography tandem mass spectrometry ( LC-MS/MS) technique. Methods:Male SD rats,aged 8-10 weeks were anaesthetized with urethane in dosage of 1.0 g/kg.A microdialysis probe was implanted into the striatum and artificial cerebrospinal fluid ( aCSF) was injected at flow rate of 2μL/min.After 1 h of aCSF perfusion,amantadine was intraperitoneally administered in dose of 1.0 mg/kg,and dialysate was instantly collected in 6 h by interval of 12 min.Amantadine concentration in the dialysate was measured using LC-MS/MS.The concentration-time profile and pharmacokinetic parameters of amantadine were calculated by DAS software .Results:The concentration-time profile of amantadine in the striatum of rats was fitted to one-compartment open model.The main pharmacokinetic parameters Tmax,Cmax,t1/2 and AUC0-∞ were (1.78±0.59)h,(38.56±9.10)μg/L,(2.07±0.35)h and (591.84±278.39)μg/(L· h) in the striatum extracellular fluid,respectively. Conclusion:We have successfully created the experimental method for studying pharmacokinetic process of amantadine in the striatum of rats using in vivo microdialysis with LC-MS/MS.This technique may provide methodology basis for research pharmacokinetics of drugs in target organs due to its simple per-formance and higher sensitivity.
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