中国药房2018，Vol.29Issue(20)：2777-2781,5.DOI:10.6039/j.issn.1001-0408.2018.20.09
马钱子碱及其纳米结构脂质载体在大鼠体内的药动学比较研究
Comparative Study on Pharmacokinetics of Brucine and Its Nanostructure Lipid Carrier in Rats
摘要
Abstract
OBJECTIVE:To establish a method for the determination of brucine concentration in plasma of rats,and to compare the pharmacokinetic differences between brucine and its nanostructure lipid carrier (NLC) in rats. METHODS:Sixteen male SD rats were randomly divided into brucine NLC solution group and brucine solution group(using normal saline as solvent, and containing brucine 1.28 mg/mL),with 8 rats in each group. They were given relevant solution 10 mg/kg via tail vein. Blood sample 0.5 mL was collected from fundus venous plexus capillary before medication and 15,20,30,40,45,60,90,120,150, 180,210,240,480 min after medication. HPLC method was adopted. The determination was performed on Dikma C18column with mobile phase consisted of methanol-water containing acetic acid and triethylamine(30∶70,V/V)at the flow rate of 1 mL/min. The detection wavelength was set at 265 nm,and column temperature was 30 ℃. Sample size was 10 μ L. Pharmacokinetic parameters of rats in 2 groups were calculated by using DAS 2.0 software,and the difference of them were compared by F test. RESULTS:The linear range of brucine plasma concentration were 1.03-66.00 μg/mL(R2＝0.999 6);the limit of quantitation was 1.03 μg/mL,and lowest detection limit was 0.515 μg/mL. RSDs of intra-day and inter-day were lower than 5%;method recoveries were 84.90%-100.88%, extraction recoveries were 80.60%-91.98%(all RSDs were lower than 10%). Average plasma concentration-time curve of single administration of brucine NLC solution and brucine solution were all in line with two-compartment model after medication via tail vein. The pharmacokinetic parameters included t1/2αwere(0.24±0.11)and(0.06± 0.03)h;t1/2 βwere (2.90 ± 0.22) and (0.57 ± 0.32)h;AUC0-twere (88.00 ± 6.98) and (28.50 ± 5.87)μg·h/mL;AUC0-∞were (109.96±7.99)and(45.06±6.66)μg·h/mL. Compared with brucine solution group,t1/2 α,t1/2 β,AUC0-tand AUC0- ∞of brucine NLC solution group were increased significantly;while CL, k10and k12were decreased significantly, with statistical significance (P＜0.05 or P＜0.01). There was no statistical significance in k21between 2 groups (P＞0.05). CONCLUSIONS: Established HPLC method is simple, specific,sensitive,precise and highly recoverable. It can be used for the determination of plasma concentration and phamacokinetic study of brucine in rats. After brucine NLC is prepared,the pharmacokinetic parameters of brucine change significantly;retention time of brucine is significantly prolonged and the clearance rate decreases significantly.关键词
马钱子碱/纳米结构脂质载体/高效液相色谱法/血药浓度/药动学/大鼠/比较研究Key words
Brucine/Nanostructure liquid carrier/HPLC/Plasma concentration/Pharmacokinetics/Rat/Comparative study分类
医药卫生引用本文复制引用
管庆霞,张悦,邹淑君,孙爽,李云行,华晓丹,杨志欣,李秀岩,王艳宏..马钱子碱及其纳米结构脂质载体在大鼠体内的药动学比较研究[J].中国药房,2018,29(20):2777-2781,5.基金项目
黑龙江省自然科学基金面上项目(No.H2016076) （No.H2016076）
黑龙江省中医药管理局中医药中青年科技攻关项目(No.ZQG-039) （No.ZQG-039）
黑龙江省教育厅科学技术研究项目(No.12531624) （No.12531624）
哈尔滨市应用技术研究与开发项目(青年后备人才A类)(No.2017RAQXJ090) （青年后备人才A类）
