三七皂苷R_1脑、血液微透析探针的体内外回收率分析  

Analysis of in Vitro and in Vivo Recovery of Brain and Blood Microdialysis Probe of Notoginsenoside R_1

作　　者：陈腾飞[1] 刘建勋[1] 姚明江[1] 宋文婷[1] 林力[1] CHEN Teng-fei LIU Jian-xun YAO Ming-jiang SONG Wen-ting LIN Li(Beijing Key Laboratory of Pharmacology of Chinese Materia Medica, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China)

机构地区：[1]中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室,北京100091

出　　处：《中国实验方剂学杂志》2017年第15期35-40,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)项目(2015-CB554405);中国中医科学院科技创新团队项目(YS1303);国家自然科学基金面上项目(81673587)

摘　　要：目的:建立三七皂苷R1脑、血液微透析探针的体内外回收率的测定方法,考察流速、药物质量浓度、探针使用次数对回收率的影响,并进行探针回收率体内稳定性研究,为三七皂苷R1的后续研究提供依据。方法:采用正透析法和反透析法进行三七皂苷R1脑、血液微透析探针体内、体外回收率的研究,采用LC-MS/MS测定微透析液中三七皂苷R1的质量浓度,计算探针回收率。结果:在流速为1.5μL·min^(-1)时,三七皂苷R1脑、血液探针体内回收率在10 h内保持稳定,平均回收率分别为14.0%和33.2%;恒定质量浓度下,探针体内外回收率均随着流速(0.5,1.0,1.5,2.0,3.0μL·min^(-1))的增加而减小,脑、血液探针的体外正透析法测得的回收率分别为(36.0±1.7)%,(23.5±1.6)%,(14.2±0.5)%,(8.0±0.7)%,(5.4±0.5)%和(61.6±2.6)%,(48.0±4.1)%,(33.0±2.8)%,(24.1±1.2)%,(18.9±1.1)%,正、反透析法所测得的探针体外回收率一致,且体内和体外回收率结果也一致;恒定流速下,三七皂苷R1质量浓度(50,200,500,1 000μg·L-1)对脑、血探针回收率均无影响;使用≤3次的探针,经过恢复处理后,仍能够保持较高的回收率。结论:反透析法测定的体外回收率与体内回收率一致,且与正透析法测定的体外回收率一致,说明反透析法能够作为研究三七皂苷R1回收率的测定方法;探针体内回收率在10 h内保持稳定,说明微透析技术能够用于三七皂苷R1脑细胞间液药代动力学、血液药代动力学的同步研究。Objective：To establish a measuring method for in vitro and in vivo recovery of microdialysis probe of notoginsenoside R1 and to investigate the effect of flow rate,drug concentration and usage count of probe on recovery,then in vivo stability of probe recovery was investigated.Method：Dialysis method and retrodialysis method were used for this study.The concentration of notoginsenoside R1 in brain and blood dialysate was determined by LC-MS/MS and the probe recovery was calculated.Result：The recovery of brain and blood microdialysis probe showed a good stability within 10 h,the average recoveries of brain and blood probe when flow velocity at 1.5 μL · min-1for notoginsenoside R1 were 14.0% and 33.2%,respectively.At the same concentration,the in vitro and in vivo recoveries of brain and blood probe of notoginsenoside R1 decreased with the increase of flow rate（0.5,1.0,1.5,2.0,3.0 μL·min-1）.The dialysis recoveries of brain and blood probe in vitro were（36.0±1.7） %,（23.5±1.6） %,（14.2±0.5） %,（8.0±0.7） %,（5.4±0.5） % and（61.6 ±2.6） %,（48.0±4.1） %,（33.0±2.8） %,（24.1±1.2） %,（18.9±1.1） %,respectively.Recoveries of dialysis and retrodialysis in vitro were approximately equal,and the recovery detected by retrodialysis in vivo was similar with the in vitro results.Concentrations（50,200,500,1 000 μg·L-1） had no obvious effect on recovery at constant flow rate.Probe which used no more than 3 times could still keep high transmittance by syringe with 2% heparin sodium and ultrapure water successively.Conclusion：Retrodialysis method can be used to study probe recovery of notoginsenoside R1,and microdialysis can be used for pharmacokinetic study of notoginsenoside R1.

关 键 词：三七皂苷R1 微透析 探针回收率 药代动力学 液相色谱-串联质谱法 

分 类 号：R283.6[医药卫生—中药学] R969.1[医药卫生—中医学]