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目的:建立测定大鼠血浆中依达拉奉的HPLC-UV法,并研究经灌胃给药后的依达拉奉在大鼠体内的药动学特征。方法:经乙酸酸化的血浆样品以高氯酸直接沉淀后,进行LC-UV法分析,色谱柱为Symmetry Shield C18(250 mm×4.6 mm,5μm),流动相为甲醇-50 mmol.L-1醋酸铵水溶液(40∶60),流速为1.0 mL.min-1,检测波长为240 nm,柱温为30℃。测定灌胃给药后大鼠血浆中依达拉奉的浓度,并计算主要药动学参数。结果:依达拉奉浓度在0.2～100.0μg.mL-1范围内线性关系良好,低、中、高3种浓度的日内日间精密度均小于10%。药动学参数:Cmax为(40.7±3.5)μg.mL-1;tmax为(0.22±0.11)h;AUC0～10为(41.6±6.1)μg.h.mL-1;AUC0～∞为(42.4±6.3)μg.h.mL-1;t1/2为(2.5±0.6)h。结论:该方法简单、灵敏,可用于依达拉奉在大鼠体内的药动学研究。
OBJECTIVE: To establish HPLC-UV method for the determination of edaravone in rat plasma and to study the pharmacokinetics of edaravone in rats after intragastric administration. Methods: After acetic acid-acidified plasma samples were directly precipitated with perchloric acid, LC-UV analysis was performed on a Symmetry Shield C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase of methanol-50 mmol·L -1 Ammonium acetate aqueous solution (40:60) was used, the flow rate was 1.0 mL.min-1, the detection wavelength was 240 nm and the column temperature was 30 ℃. The concentration of edaravone in rat plasma after intragastric administration was determined and the main pharmacokinetic parameters were calculated. Results: Edaravone concentration was good in the range of 0.2-100.0μg.mL-1. The intra-day and inter-day precision of low, medium and high concentrations were all less than 10%. Pharmacokinetic parameters: Cmax was (40.7 ± 3.5) μg.mL-1; tmax was (0.22 ± 0.11) h; AUC0-10 was (41.6 ± 6.1) μg.h.mL-1; ± 6.3) μg.h.mL-1; t1 / 2 was (2.5 ± 0.6) h. Conclusion: This method is simple and sensitive and can be used to study the pharmacokinetics of edaravone in rats.