Page 23 - 《中国药房》2021年3期

·药学研究·

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 Δ

1＊
1，2 #
戴秋阳 ，汤 米 ，张培炎 ，包小峰 ，陈 勇 （1.南通大学药学院药剂系，江苏 南通 226001；2.南通联科药
1
1
1
业有限公司，江苏 南通 226009）
中图分类号 R969.1 文献标志码 A 文章编号 1001-0408（2021）03-0273-05
DOI 10.6039/j.issn.1001-0408.2021.03.04

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
10 μL。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0.02～8.00 μg/mL（r分别为0.999 6、0.999 4），
定量下限均为0.02 μg/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。
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

Comparison of the Concentrations of Stiripentol and Its Self-nanoemulsifying Drug Delivery System in
Plasma and Brain of Rats
DAI Qiuyang ，TANG Mi ，ZHANG Peiyan ，BAO Xiaofeng ，CHEN Yong （1. Dept. of Pharmacy，School of
1，2
1
1
1
1
Pharmacy，Nantong University，Jiangsu Nantong 226001，China；2. Novast Pharmaceuticals，Ltd.，Jiangsu
Nantong 226009，China）
ABSTRACT 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 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.
Δ 基金项目：国家自然科学基金资助项目（No.81603044）；中国博 The concentration of STP in plasma and brain tissue is
士后科学基金资助项目（No.2017M611886）
increased after STP is made into SNEDDS.
＊硕士研究生。研究方向：新型制剂及分析。E-mail：dqy_2018@
KEYWORDS Stiripentol；Self-nanoemulsifying drug delivery
163.com
# 通信作者：副教授，硕士生导师，博士。研究方向：药剂学。 system； HPLC-fluorescence method； Drug distribution in
E-mail：scuchen2003@163.com vivo；Plasma；Cerebral tissue

中国药房 2021年第32卷第3期 China Pharmacy 2021 Vol. 32 No. 3 ·273 ·