王健,孙瑜,宋丽丽,庄朋伟,陈磊,乔夕,黎明修,金宗英,王美娜.芒柄花素磺酸钠在脑缺血再灌注大鼠体内的药动学研究[J].现代药物与临床,2019,34(5):1285-1289
芒柄花素磺酸钠在脑缺血再灌注大鼠体内的药动学研究
Pharmacokinetics of sodium formononetin-3'-sulphonate in cerebral ischemia- reperfusion rat
投稿时间:2018-12-25  
DOI:10.7501/j.issn.1674-5515.2019.05.004
中文关键词:  芒柄花素磺酸钠  脑缺血再灌注  血浆药动学  高效液相色谱法
英文关键词:sodium formononetin-3'-sulphonate  cerebral ischemia- reperfusion  plasma pharmacokinetics  HPLC
基金项目:天津市卫生和计划生育委员会中医中西医结合科研课题(2017104)
作者单位E-mail
王健 天津市儿童医院, 天津 300074  
孙瑜 天津中医药大学, 天津 301617 sunrain806@163.com 
宋丽丽 天津中医药大学, 天津 301617  
庄朋伟 天津中医药大学, 天津 301617  
陈磊 天津中医药大学, 天津 301617  
乔夕 天津中医药大学, 天津 301617  
黎明修 天津中医药大学, 天津 301617  
金宗英 天津中医药大学, 天津 301617  
王美娜 天津中医药大学, 天津 301617  
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中文摘要:
      目的 建立芒柄花素磺酸钠血浆样品的高效液相色谱(HPLC)分析方法,并应用该方法对正常大鼠和模型大鼠体内的芒柄花素磺酸钠进行药动学分析;明确芒柄花素磺酸钠在正常、模型大鼠血浆中的吸收分布情况。方法 采用Venusil MP C18色谱柱(250 mm×4.6 mm,5 μm),流动相乙腈–水(30∶70,水相中加0.1%甲酸),柱温30℃,进样量20.0 μL,体积流量1.0 mL/min,检测波长250 nm。制备大鼠脑缺血再灌注模型,将SD大鼠随机分为10组,每组5只大鼠。于大鼠脑缺血1 h及再灌注3.5 h按20 mg/kg ip芒柄花素磺酸钠注射液,并于给药后15、30、45、60、90、120、150、180、240、300 min腹主动脉取血。正常组大鼠分别于给药后5、10、15、30、45、60、90、120、150、180、240、300、480、720 min目内眦取血。样品经处理后,采用HPLC法检测各时间点血浆中的芒柄花素磺酸钠浓度。采用药动学软件WinNonLin 6.3进行数据分析,计算药动学参数。结果 芒柄花素磺酸钠在0.25~100.0 μg/mL线性关系良好。定量下限RSD值为12.15%。日内精密度RSD值均<5.0%,日间精密度RSD值均<10.0%。提取回收率均>80%,RSD值均<5.0%。芒柄花素磺酸钠在正常大鼠、模型大鼠血浆内药动学参数为:t1/2分别为(173.13±13.12)min、(117.86±45.05)min,Cmax分别为(67.23±4.04)μg/mL、(75.22±10.57)μg/mL,AUC0-t分别为(2 493.69±216.98)min·μg/mL、(6 094.52±250.81)min·μg/mL,Vd分别为(1 981.97±134.12)mL/kg、(484.56±167.93)mL/kg,Cl分别为(7.96±0.73)mL·min/kg、(2.87±0.14)mL·min/kg,MRT0-t分别为(76.92±1.54)min、(89.06±0.77)min。结论 应用HPLC法测定芒柄花素磺酸钠的血药浓度定量准确、灵敏,芒柄花素磺酸钠在模型大鼠血浆中吸收的量多,单位时间内消除的量少,滞留时间长。
英文摘要:
      Objective To establish an HPLC analysis method for sodium formononetin-3'-sulphonate plasma samples, and the method was applied to the pharmacokinetic analysis of sodium formononetin-3'-sulphonate in normal rats and model rats. The absorption and distribution of sodium formononetin-3'-sulphonate in plasma of normal and model rats were determined. Methods The separation was performed on Venusil MP C18 column (250 mm×4.6 mm, 5 μm). The mobile phase consisted of acetonitrile-water (30:70, add 0.1% formic acid to the aqueous phase). Temperature of column was set at 30℃, and the injection volume was 20.0 μL. The flow rate was 1.0 mL/min, and the detective wavelength was set at 250 nm. Rat cerebral ischemia reperfusion models were established. SD rats were randomly divided into 10 groups, and each group had 5 rats. At the time point of 1 h after cerebral ischemia and 3.5 h after reperfusion, rats were ip administered with sodium formononetin-3'-sulphonate injection 20 mg/kg, and the abdominal aorta blood samples were taken at 15, 30, 45, 60, 90, 120, 150, 180, 240, and 300 min after administration. Rats in the normal group were collected the inner canthus blood at the time of 5, 10, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 480, and 720 min after the administration. Samples were treated, and HPLC method was used to detect sodium formononetin-3'-sulphonate concentration in plasma at different time points. Pharmacokinetic data were analyzed by WinNonLin 6.3 pharmacokinetic software, and pharmacokinetic parameters were calculated. Results A good linearity was shown in the concentration ranges of 0.25 -100.0 μg/mL for sodium formononetin- 3'-sulphonate, and RSD value of the quantitative limits was 12.15%. The RSD value of inter-day precisions were less than 5.0%, and the intra-day precisions were less than 10.0%. The recovery rate of extraction was over 80%, and RSD value was less than 5.0%. The pharmacokinetic parameters of sodium formononetin-3'-sulphonate in plasma of normal rats and model rats were as following:t1/2 were (173.13 ±13.12) and (117.86 ±45.05) min, Cmax were (67.23 ±4.04) and (75.22 ±10.57) ?g/mL, AUC0-t were (2 493.69 ±216.98) and (6 094.52 ±250.81) min·?g/mL, Vd were (1 981.97 ±134.12) and (484.56 ±167.93) mL/kg, Cl were (7.96 ±0.73) and (2.87 ±0.14) mL·min/kg, MRT0-t were (76.92 ±1.54) and (89.06 ±0.77) min. Conclusion The determination of sodium formononetin-3'-sulphonate in blood by HPLC is accurate and sensitive. And the amount of sodium formononetin-3'-sulphonate absorbed in the plasma of model rats is large, the amount eliminated in unit time is small, and the retention time is long.
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