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目的:建立HPLC法用于测定大鼠血浆中葛根素的浓度,并研究格列本脲对葛根素在大鼠体内药动学行为的影响。方法:将18只大鼠分成3组:第1组葛根素单独给药组;第2组先给格列本脲,1.5 h后给予葛根素;第3组先给葛根素,0.5 h后给予格列本脲。血浆样品用3倍量乙腈沉淀蛋白,进样分析。色谱柱为Diamonsil C18(200 mm×4.6 mm,5μm),流动相为乙腈-0.5%醋酸水(14∶86),柱温30℃,检测波长249 nm。结果:葛根素血浆浓度的线性范围为0.045 0~3.60μg·m L-1(r>0.998),定量下限为0.045 0μg·m L-1。日内和日间精密度(RSD)均小于13%,准确度(RE)在1.1%~14%。与单独给药组相比,第2组葛根素的Cmax升高了71.9%(P<0.01),AUC0~t和AUC0~∞分别增加了34.9%和36.0%(P<0.05);第3组葛根素的药动学参数无明显变化(P>0.05)。结论:推测格列本脲在大鼠体内可能促进葛根素的吸收或抑制其代谢,而对其消除过程无明显影响。
OBJECTIVE: To establish an HPLC method for the determination of puerarin in rat plasma and to study the effect of glyburide on pharmacokinetics of puerarin in rats. METHODS: Eighteen rats were divided into three groups: Group 1 received puerarin alone; Group 2 received glibenclamide and puerarin after 1.5 h; Group 3 received puerarin for 0.5 h Glibenclamide. Plasma samples were precipitated with 3 volumes of acetonitrile and analyzed by injection. The column was Diamonsil C18 (200 mm × 4.6 mm, 5 μm). The mobile phase was acetonitrile-0.5% acetic acid water (14:86). The column temperature was 30 ℃ and the detection wavelength was 249 nm. Results: The linear range of plasma puerarin was 0.045 0 ~ 3.60 μg · m L -1 (r> 0.998). The lower limit of quantification was 0.045 0 μg · m L -1. The intra- and inter-day precision (RSD) was less than 13% and the accuracy (RE) was 1.1% ~ 14%. The Cmax of puerarin in Group 2 increased by 71.9% (P <0.01) and the AUC0 ~ t and AUC0 ~ ∞ increased by 34.9% and 36.0%, respectively (P <0.05) Pharmacokinetic parameters of puerarin had no significant changes (P> 0.05). Conclusion: It is speculated that glibenclamide may promote the absorption of Puerarin in rats or inhibit its metabolism without any significant effect on its elimination process.