氟阿普唑仑在大鼠体内分布及代谢降解规律研究

Distribution and Metabolic Pathway of Flualprazolam in Rat

目的研究氟阿普唑仑及其主要代谢物α-羟基氟阿普唑仑在大鼠体内分布及代谢规律。方法40只SD大鼠随机分为4组,禁食12h,第一组按0.45mg/kg氟阿普唑仑灌胃给药后不同时间点采集大鼠尾静脉血,并收集每天尿液;第二组为血液实验空白对照组;第三组给药0.25h后处死,取血、心、肝、肺、肾、脑、脾、肌肉,经快速溶剂萃取提取后用高效液相色谱-三重四极杆质谱检测氟阿普唑仑及α-羟基氟阿普唑仑含量;第四组为分布实验空白对照组。结果氟阿普唑仑进入体内后,迅速分布代谢,在0.25h内达到血液最高浓度。氟阿普唑仑在各器官中的分布特点为:肾>脑>心>肝>肌肉>脾>肺>血,α-羟基氟阿普唑的分布特点为:肝>肾>心>脾>肺>肌肉>血>脑。结论本研究监测了氟阿普唑仑及主要代谢物在大鼠体内的分布及降解规律,为氟阿普唑仑的体内检验及体内过程分析提供科学依据。

Objective To probe into the distribution and metabolic pathway of flualprazolam plus its main metabolite(α–hydroxylflualprazolam)in rat.Methods 40 SD rats were randomly divided into 4 groups and fasted for 12 hours,with the first group being fed of flualprazolam by gavage as per 0.45 mg/kg and having their respective blood collected from tail vein at different time and each one’s urine received every day after administration.The second group was taken as the blank control to the first one.The third group was executed at 0.25h after drug administration,having their respective blood,heart,liver,lung,kidney,brain,spleen and muscle collected and extracted with rapid solvent extraction.The fourth group was the blank control against the third one.The distributing and metabolizing flualprazolam andα-hydroxyflualprazolam were detected through HPLC-MS/MS.Results Flualprazolam was found of rapid distributing and metabolizing in rats,reaching its highest blood concentration within 0.25h,having shown its sequential distribution in various organs as follows:kidney>brain>heart>liver>spleen>muscle>muscle>lung>blood.Yet,α-hydroxyflualprazolam demonstrated its discrepant organ-specific distributing order:liver>kidney>heart>spleen>lung>muscle>blood>brain.Conclusion The experiment has showed the distribution and degradation of flualprazolam and its main metabolite in rats who were administered of flualprazolam by gavage,capable of providing scientific basis for flualprazolam to test in vivo and have its metabolic pathway analyzed.