摘要
目的:建立测定大鼠血浆和脑组织中司替戊醇(STP)质量浓度的方法,并比较STP及其自纳米乳在血浆、脑组织中的药物浓度。方法:以占吨酮为内标,采用高效液相色谱-荧光检测法(HPLC-FLR)测定。色谱柱为Diamonsil C18,流动相为乙腈-25 mmol/L KH2PO4水溶液[44∶56(V/V),pH 2.6],流速为1.5 mL/min,激发波长为210 nm,发射波长为400 nm,柱温为30℃,进样量为10μL。将36只大鼠随机分为两组,每组18只,分别灌胃STP自纳米乳和STP混悬液(40 mg/kg,均以STP计)。于给药后0.5、1、2 h时采集大鼠血液和脑组织样品(各时间点每组各6只),经乙腈沉淀蛋白(脑组织需先进行匀质)等处理后,采用上述色谱条件检测STP的质量浓度并比较。结果:STP在血浆、脑组织中药物浓度检测的线性范围均为0.02~8.00μg/mL(r分别为0.9996、0.9994),定量下限均为0.02μg/mL;日内、日间RSD均小于5%,提取回收率和方法回收率均不低于90%。与STP混悬液组比较,STP自纳米乳组大鼠各时间点的血药浓度(给药后1 h除外)、脑组织中药物浓度(给药后2 h除外)均显著升高(P<0.05),且两者(以STP自纳米乳为对象)具有明显的线性关系。结论:所建HPLC-FLR法的灵敏度、精密度较高,可用于研究STP及其自纳米乳在大鼠血浆和脑组织中的分布情况;将STP制成自纳米乳后,其在血浆、脑组织中的药物浓度明显提高。
OBJECTIVE:To establish a method for determining stiripentol(STP)concentration in plasma and brain of rats,and to compare the concentrations of STP and its self-nanoemulsifying drug delivery system(STP-SNEDDS)in plasma and brain.METHODS:Using xanthone as internal standard,HPLC-fluorescence(HPLC-FLR)method was adopted.The determination was performed on Diamonsil C18 column with mobile phase consisted of acetonitrile-25 mmol/L KH2PO4 solution[44∶56(V/V),pH 2.6]at a flow rate of 1.5 mL/min;the excitation and emission wavelengths were 210 nm and 400 nm,respectively;the column temperature was 30℃;the sample size was 10μL.Totally 36 rats were randomly divided into 2 groups,with 18 rats in each group.They were given STP-SNEDDS and STP suspension(40 mg/kg,by STP)intragastrically.Blood and brain tissue samples were collected at 0.5,1,2 h after administration(6 rats in each group at different time point).After the protein was precipitated by acetonitrile(brain tissue should be homogenized),the concentrations of STP were determined by the above chromatographic conditions.RESULTS:The linear ranges of STP concentration in plasma and brain tissue were 0.02-8.00μg/mL(r were 0.9996,0.9994,respectively).The limits of quantitation were both 0.02μg/mL.The inter-day and intra-day RSDs were all less than 5%.The extraction recovery and method recovery were all no less than 90%.Compared with STP suspension group,the plasma concentration(except for 1 h after administration)and cerebral concentration(except for 2 h after administration)of STP in STP-SNEDDS group were all significantly increased(P<0.05),showing significant linear relationship between them(for STP-SNEDDS).CONCLUSIONS:Established HPLC-FLR method presents high accuracy and precision,and can be used for the distribution of STP and STP-SNEDDS in plasma and brain.The concentration of STP in plasma and brain tissue is increased after STP is made into SNEDDS.
作者
戴秋阳
汤米
张培炎
包小峰
陈勇
DAI Qiuyang;TANG Mi;ZHANG Peiyan;BAO Xiaofeng;CHEN Yong(Dept.of Pharmacy,School of Pharmacy,Nantong University,Jiangsu Nantong 226001,China;Novast Pharmaceuticals,Ltd.,Jiangsu Nantong 226009,China)
出处
《中国药房》
CAS
北大核心
2021年第3期273-277,共5页
China Pharmacy
基金
国家自然科学基金资助项目(No.81603044)
中国博士后科学基金资助项目(No.2017M611886)。
关键词
司替戊醇
自纳米乳
高效液相色谱-荧光检测法
体内药物分布
血浆
脑组织
Stiripentol
Self-nanoemulsifying drug delivery system
HPLC-fluorescence method
Drug distribution in vivo
Plasma
Cerebral tissue
