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目的建立大鼠血浆中田蓟苷含量的HPLC测定方法,并应用于田蓟苷在大鼠体内的药代动力学研究。方法色谱柱为AgilentC18(4.6 mm×250mm,5μm),流动相为乙腈-0.4%磷酸水(34:66),流速1.0mL·min-1,检测波长327nm,柱温35℃。采用HPLC法测定给药后大鼠血浆中田蓟苷的浓度,采用DAS2.0软件拟合并计算其药代动力学参数。结果大鼠血浆中田蓟苷在0.031~1.984μg·mL-1范围内线性关系良好(r=0.9990),日内及日间精密度小于6%,方法回收率大于96%。提取回收率大于80%,符合生物样品分析要求。大鼠灌胃田蓟苷3个剂量(25,50,100mg·kg-1)后,t1/2β分别为(6.324±0.319),(6.099±1.464),(9.296±2.218)h;AUC(0-t)分别为(0.658±0.019),(1.050±0.056),(1.380±0.043)mg·L-1·h-1;Tmax分别为(0.278±0.127),(0.306±0.096),(0.361±0.048)h;Cmax分别为(0.314±0.016),(0.566±0.031),(0.747±0.050)mg·L-1。结论该法灵敏度高,专属性强,准确可靠,适用于田蓟苷大鼠血药浓度的测定及其药代动力学研究。
OBJECTIVE To establish a method for the determination of thymidine in plasma of rats by HPLC and to study the pharmacokinetics of thymidine in rats. Methods The column was Agilent C18 (4.6 mm × 250 mm, 5 μm). The mobile phase consisted of acetonitrile-0.4% phosphoric acid water (34:66), the flow rate was 1.0 mL · min-1, the detection wavelength was 327 nm and the column temperature was 35 ℃. The plasma concentration of thymidine in the plasma was determined by HPLC. The pharmacokinetic parameters were calculated by DAS2.0 software. Results There was a good linear relationship (r = 0.9990) in the range of 0.031-1.984 μg · mL-1. The intra-day and inter-day precision was less than 6%. The method recovery was more than 96%. Extraction recovery greater than 80%, in line with the biological sample analysis requirements. After administration of thymidine at three doses (25, 50 and 100 mg · kg -1), the t1 / 2β were (6.324 ± 0.319), (6.099 ± 1.464) and (9.296 ± 2.218) t were (0.658 ± 0.019), (1.050 ± 0.056) and (1.380 ± 0.043) mg · L-1 · h-1, respectively; Tmax were (0.278 ± 0.127), (0.306 ± 0.096) and (0.361 ± 0.048 ) h and Cmax were (0.314 ± 0.016), (0.566 ± 0.031) and (0.747 ± 0.050) mg · L -1, respectively. Conclusion The method has high sensitivity, specificity, accuracy and reliability, and is suitable for the determination of thimerosal in rats and its pharmacokinetics.