摘要
建立了小鼠血浆和脑中丹参酮ⅡA(TsⅡA)的高效液相色谱分析法,并用于测定静脉给药后小鼠血浆和脑中TsⅡA浓度的动态变化及药动学参数。小鼠尾静脉注射TsⅡA单体8.0mg/kg,血浆及脑样品经乙酸乙酯萃取后,用HPLC法检测。所建立的血浆样品分析方法线性范围为0.05~7.12mg/L,相关系数r=0.9984;脑样品分析方法线性范围为0.022~2.37mg/L,相关系数r=0.9988;血浆和脑样品中最低定量限分别为0.0498和0.022mg/L;检出限分别为0.0255和0.0166mg,/L;日内和日间RSD〈10.3%。本方法专属、准确、灵敏,可以定量检测小鼠静脉注射后TsⅡA在血和脑中的浓度。TsⅡA静脉给药后,小鼠血浆中TsⅡA浓度-时间变化可用三室模型拟合,峰浓度为1.58mg/L,AUC(04)值为68.18mg/L·min。给药后5min Ts ⅡA在小鼠脑中即可达峰值0.17mg/L,且480min时仍能在脑组织中测到,表明TsⅡA能很快透过血脑屏障,且能在脑组织中停留较长时间。
HPLC method was developed to measure the concentration of tanshinone ⅡA (TsⅡA) in mouse plasma and brain. The method was applied to preliminary study on pharmacokinetics of TsⅡA in mouse plasma and brain. After an administration of 8.0 mg/kg TsⅡA by intravenous injection, plasma and brain samples were collected and extracted by liquid-liquid extraction with ethyl acetate and determined by HPLC. The i method has a linear range from 0. 0498 to 7.12 mg/L with correlation coefficients of 0. 9984 in plasma and a linear range from 0. 022 to 2.37 mg/L with correlation coefficients of 0. 9988 in brain. The limits of quantitation(LOQs) in plasma and brain were 0.0498 and 0.022 mg/L respectively, and the limits of detection (LODs) were 0.0255 and 0.0166 mg/L respectively. The intra-day and inter-day RSDs were less than 10.3%. The developed method was specific, accurate and sensitive. The plasma concentration-time curve was fitted as three-compartment model. The peak concentration of TsⅡA in mouse plasma was 1.58 mg/L, and the value of AUC(0-t) was 68.18 mg/L·min. The concentration of TsⅡA in mouse brain achieved the peak value of 0.17 mg/L 5 rain after intravenous administration and could be still detected in brain after 480 min. The results indicated that TsⅡA readily penetrated the blood-brain barrier and could be stay in the brain for a long time.
出处
《分析化学》
SCIE
EI
CAS
CSCD
北大核心
2008年第12期1677-1682,共6页
Chinese Journal of Analytical Chemistry
基金
国家"十一五"科技支撑计划(No.2006BAI14B05)资助项目
关键词
丹参酮ⅡA
高效液相色谱法
药代动力学
小鼠
血浆
脑
Tanshinone ⅡA, high performance liquid chromatography, pharmacokinetics, mouse, plasma,brain