摘要
采用以稳定同位素为内标的微透析技术,研究清醒自由活动下大鼠脑局部药动学过程。健康SD大鼠为研究对象,以尼古丁(nicotine)为模型药物,以氘代尼古丁(deuterium labeled nicotine,DL-nicotine)为微透析(microdialysis,MD)的内标物。样品采用LC-MS/MS法检测,同时测定透析液中尼古丁及DL-尼古丁的浓度。数据分析采用DAS2.0软件。经皮给予尼古丁后,大鼠脑局部尼古丁的吸收和分布过程符合二室模型,其中t1/2α为170.31 min,t1/2β为263.30 min,AUC0-∞为2.75×105μg.L-1.min。DL-尼古丁可作为尼古丁的内标物进行探针回收率的校正;稳定同位素内标微透析技术可实现尼古丁在清醒状态大鼠脑局部药动学的研究,为戒烟方法的寻找及尼古丁经皮制剂的药动学-药效学相结合的研究提供了新思路。
The paper is to report the study of pharmacokinetics of transdermal administered nicotine in the brain of freely moving rat by using microdialysis with stable labeled isotope as internal standard.The pharmacokinetic behavior of nicotine in Sprague Dawley rat brain was investigated after intranasal administration（3.75 mg）.Brain fluid samples were collected by intracerebral microdialysis with DL-nicotine as internal standard.Concentrations of nicotine and DL-nicotine in the sample were measured by HPLC-MS/MS.Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software.The recovery of nicotine and the delivery of DL-nicotine were the same.The fate of absorption and distribution was two compartment model and the values of t1/2α was 170.31 min,t1/2β was 263.30 min and the AUC0-∞ was 2.75×105 μg·L-1·min separately.DL-nicotine can be used to calibrate the recovery of nicotine,and the new method of stable isotope microdialysis can be used to study the pharmacokinetics of freely moving rat.It will make sense for the treatment of addiction of tobacco and provide a new thought for the research of pharmacokinetics-pharmacodynamic combination.
出处
《药学学报》
CAS
CSCD
北大核心
2011年第3期333-337,共5页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(3077279130701097)
广东省科技计划项目(2010B030700035)
关键词
微透析
稳定同位素
尼古丁
氘代尼古丁
药动学
microdialysis
stable labeled isotope
nicotine
DL-nicotine
pharmacokinetics
