摘要
目的为龙胆苦苷(Gent)的血脑屏障通透性提供直接证据,并阐明其在脑组织中的药物动力学特征。方法建立小鼠脑脊液、脑组织和血浆中龙胆苦苷含量测定的LC-MS/MS方法;直接测定小鼠腹腔注射龙胆苦苷后脑脊液中的药物浓度;建立脑组织和血浆中龙胆苦苷的药-时曲线,并比较药物动力学参数。结果 Gent在血浆样本检测限均为10 ng·ml-1,脑组织样本中的检测限为10 ng·g-1,脑脊液样本中检测限为2.5 ng·ml-1。小鼠腹腔注射50 mg·kg-1龙胆苦苷后0.5 h和2 h,在脑脊液中均能检测到原型药物;龙胆苦苷在血浆中的Cmax为57.43μg·ml-1,在脑组织中的Cmax为0.45μg·g-1;在脑组织中的平均滞留时间MRT0-∞为294.68 min,在血浆中的MRT0-∞为45.62 min。结论龙胆苦苷能够通过血脑屏障,在脑组织中代谢消除相对较慢。
Objective To clarify the blood - brain bawler permeability of Gentiopicroside and investigate its pharmacodynamic characteristics in the brain tissue. Methods A rapid and sensitive liquid chromatography/tandem mass spectrometry （ LC - MS/ MS ） method was developed to determine Gentiopicroside concentrations in mouse plasma, brain homogenate and cerebrospinal flu- id for the first time in the present paper. Blood - brain permeability was evaluated by Gentiopicroside concentrations in ccrebrospi- nal fluid following i. p. administration of 50 mg kg-1 Gentiopicroside; pharmacokinetic parameters in brain and plasma were cal- culated by DAS 2.0 software. Results The limit of detection for Gentiopicroside is 10 ng mL-1 in mouse plasma, 10 ng g-1 in brain homogenate and 2.5 ng mL-1 in eerebrospinal fluid, respectively. Gentiopicroside could be detected in cerebrospinal fluid 0.5 h and 2 h following one dose of i. p. administration. The main pharmacokinetic parameters are summarized as follows ： C in plasma = 57.43 μg mL - 1 ; Cmax in brain homogenate = 0.45 μg g- 1 ; MRT 0 - 1 in plasma = 45.62 min ; MRT 0-∞ in brain homogenate = 294.68 min. Conclusion The results indicated that Gentiopicroside could cross the blood - brain - barrier and the MRT is longer in brain tissue than in plasma.
出处
《时珍国医国药》
CAS
CSCD
北大核心
2018年第1期14-17,共4页
Lishizhen Medicine and Materia Medica Research
基金
国家自然科学基金(81403064)
陕西省科技厅社会发展科技攻关项目(2016SF-107)
西安医学院博士科研启动基金项目(2016DOC23)
