HPLC法测定阿魏酸钠在Beagle犬体内血浆浓度及药动学研究

Study on the Plasma Concentration of Sodium Ferulate by HPLC and Its Pharmacokinetics in Beagle Dogs

目的:建立测定血浆中阿魏酸钠浓度的HPLC法,并用于阿魏酸钠片剂在Beagle犬体内的药代动力学研究。方法:色谱柱为Diamonsil(TM)C18柱,250mm×4.6mm,5μm,流动相为乙腈-水-冰乙酸(25∶74.2∶0.8),流速为1.0mL/min,检测波长为320nm。以替硝唑为内标,用乙腈处理血浆样品,震荡离心分离上清液进样。结果:标准曲线线性范围0.025～1.80mg/L,r=0.9995。阿魏酸钠平均回收率99.6%,最低检测浓度为5.25μg/L,日内、日间RSD<5.3%。阿魏酸钠片剂在Beagle犬体内的血药浓度-时间过程符合一房室模型,T1/2(ka)为10.88min,T1/2(ke)为29.78min。结论:HPLC法方法简便、快速、重现性好,适用于阿魏酸钠血药浓度测定及药代动力学研究。

Objective： To develop a HPLC method to determine the plasma concentration of sodium ferulate and study the pharmacokinetics in beagle dogs. Methods： Diamonsil （TM） C18 was used as the analytical column （250 mm×4.6 mm, 5 μm）. The mobile phase was acetonitrile -water-acetic acid （25：74.2：0.8）. The flow rate was 1.0 mL/min and detection wave length was 320 nm. Plasma samples were prepared for analysis by internal standard （Tinidazole） followed by extracting with acetonitrile. Results： Linear calibration curve was obtained by plotting concentration with peak area ratio over the range of 0.025-1.80 mg/L with a correlation coefficient of 0.999 5. The average recovery of sodium ferulate was 99.6%. The minimum detectable concentration of sodium ferulate was 5.25μg/L. The relative standard deviations of within-day and between-days were less than 5.3% respectively. The plasma concentration-time curve of sodium ferulate oral tablet was found to be onecompartment model with T（1/2）ka of 10.88min and T（1/2）ka of 29.78 rain in beagle dogs. Conclusion： The method is simple, rapid, accurate and precise, and it can be used for the determination of plasma concentration of sodium ferulate and the study of its pharmacokinetics.