益母草碱口服油包油微乳在大鼠体内的药动学研究

Study on Pharmacokinetics of Leonurine in Rats after Intragastric Administration of Leonurine O/O Microemulsion

目的：建立测定大鼠益母草碱（LE）血浆浓度的方法,并用于大鼠灌胃LE口服油包油（O/O）型微乳（ME）后的药动学研究。方法：采用反相高效液相色谱法。色谱柱为ZORBAX SB-C18,流动相为甲醇-水（50∶50,V/V）,流速为1.0 ml/min,检测波长为277 nm,柱温为30℃,进样量为20μl。12只SD大鼠随机均分为LE-ME（300 mg/kg）组和益母草碱混悬液（LE-SWW,300 mg/kg）组,LE-ME组大鼠灌胃给药15、30、60、90、120、180、240、360、480、720、1 440 min,LE-SWW组大鼠灌胃给药10、30、60、90、120、150、180、240、360、480、720 min后眼眶采血测定血药浓度,计算药动学参数。结果：LE质量浓度在0.010-10.000μg/ml范围内与峰面积积分值呈良好线性关系（r=0.999 6）,精密度试验的RSD值均小于7.2%,1方法回收率为94.86%-101-27%,提取回收率为76.91%-80.02%,稳定性试验的RSD均小于2.75%。与LE-SWW组比较,LE-ME组cmax增加至1.46倍,t1/2延长至3.65倍,AUC0-∞增加至6.11倍,体内平均滞留时间（MRT）提高至4.15倍（P〈0.05）,相对生物利用度为610.65%。结果：该方法可靠、灵敏、简便。与LE-SWW比较,LE-ME能明显延长LE在大鼠体内的滞留时间,明显提高生物利用度。

OBJECTIVE： To establish the method for the plasma concentration of leonurine （LE） in rats and pharmacokinetic study of LE in rats after intragastric administration of Leonurine O/O microemulsion （LE-ME）. METHODS： RP-HPLC method was adopted. The determination was performed on ZORBAX SB-C18, column with mobile phase consisted of methanol-water （50 ： 50, V/V） at the flow rate of 1.0 ml/min. The detection wavelength was set at 277 nm and column temperature was 30 ℃. The sam- ple size was 20 μl. 12 SD rats were randomly divided into LE-ME group （300 mg/kg） and Leonurine suspension group （LE- SWW, 300 mg/kg）. LE-ME group was given LE-ME intragastrically for 15, 30, 60, 90, 120, 180, 240, 360, 480, 720 and 1 440 lain, respectively; LE-SWW group was given LE-SWW intragastrically for 10, 30, 60, 90, 120, 150, 180, 240, 360, 480 and 720 min, respectively. The blood samples were collected from eye socket at different time points to determine plasma concentrations, and then pharmacokinetic parameters were calculated. RESULTS： The linear range of LE was 0.010-10.000 μg/ml （r----- 0.999 6） with method recoveries of 94.86%-101-27% and extretion recoveries of 76.91%-80.02%. RSD of precision and stability tests were lower than 7.2% and 2.75%. Comparison with LE-SWW group, Cmax was increased to 1.46 times, t1/2 prolonged to 3.65 times, AUC0increased to 6.11 times and mean residence time （MRT） increased to 4.15 times （P〈0.05）, and the relative bio- availability was 610.65%. CONCLUSIONS： The method is reliable, sensitive and convenient. Compared with LE-SWW, LE-ME could significantly prolong the residence time and increase the bioavailability of LE in rats.