Comparison of the Concentrations of Stiripentol and Its Self-nanoemulsifying Drug Delivery System in Plasma and Brain of Rats
- VernacularTitle:司替戊醇及其自纳米乳在大鼠血浆和脑组织中的药物浓度比较
- Author:
Qiuyang DAI
1
;
Mi TANG
1
;
Peiyan ZHANG
1
;
Xiaofeng BAO
1
;
Yong CHEN
1
Author Information
1. Dept. of Pharmacy，School of Pharmacy，Nantong University，Jiangsu Nantong 226001，China
- Publication Type:Journal Article
- Keywords:
Stiripentol;
Self-nanoemulsifying drug delivery
- From:
China Pharmacy
2021;32(3):273-277
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To establish a method for de termining 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 C 18 column with mobile phase consisted of acetonitrile- 25 mmol/L KH 2PO4 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 10 μL. 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 0.02-8.00 μg/mL（r were 0.999 6， 0.999 4，respectively）. The limits of quantitation were both 0.02 μg/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 isincreased after STP is made into SNEDDS.
