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目的 :建立测定依托度酸浓度的高效液相色谱法并研究该药在大鼠体内的药动学。方法 :血浆 2 0 0 μL加入 1 0 0mg·L-1 内标 (奥沙普秦) 50 μL ,酸化后用乙酸乙酯∶正己烷 (1∶1 9)提取。采用C1 8分析柱 ,以乙腈∶水∶三乙胺 (1 6∶84∶0 .0 0 2 )为流动相 ,流速为 1 .0mL·min-1 ;检测波长 2 80nm。大鼠按依托度酸 2 0mg·kg-1 剂量灌胃 ,给药前及给药后 5 ,1 0 ,2 0 ,30min和 1 ,3,6 ,1 2 ,2 4 ,48,72h采血 ,测定血浆药物浓度。绘制血药浓度 -时间曲线图并计算主要药动学参数。结果 :依托度酸与内标物的保留时间分别为 5 .2 8min和 6 .80min ;依托度酸浓度在1 .0～ 1 0 0 .0mg·L-1 范围内与依托度酸/内标物的峰面积比呈良好线性关系 ,回归方程为 :Y =0 .0 32 2 7C +0 .0 0 1 2 8,r =0 .9999,n =7。本法高、中、低浓度的绝对回收率为 73 .4 %～ 80 .5 % ,方法回收率在 97.3%～1 0 6.0 % ,日内RSD <4% ,日间RSD <8%。依托度酸的药动学参数为Tmax=0 .2 8h± 0 .1 3h ;Cmax=69mg·L-1 ± 5mg·L-1 ;T1 /2 =1 6 .9h± 2 .1h ;AUC =2 31 4mg·h·L-1 ±32 8mg·h·L-1 。结论 :本法快捷、灵敏、准确、重复性好 ,适用于依托度酸血药浓度测定及药动学研究。
Objective: To establish a HPLC method for the determination of the concentration of etodolac and to study its pharmacokinetics in rats. Methods: 200 μL of plasma was added to 50 μL of internal standard (oxaprozin) of 100 mg · L -1 and acidified and extracted with ethyl acetate: n-hexane (1:19). The mobile phase consisted of acetonitrile and water: triethylamine (16:84:0.O 0 2) with a mobile phase of C1 8 at a flow rate of 1.0 mL · min-1 and a detection wavelength of 280 nm. The rats were administered intragastrically with 20 mg · kg -1 of etodolac and the blood samples were taken at 5,10, 20,30 minutes and 1,3,6, 12,4,48 and 72 hours after drug administration, Determination of plasma drug concentration. Draw a plasma concentration-time curve and calculate the main pharmacokinetic parameters. Results: The retention time of etodolac and internal standard were respectively 5.28min and 6.80min; the concentration of etodolac was in the range of 1.0 ~ 10.0 mg · L-1 with etodolac / The peak area ratio showed a good linear relationship, the regression equation is: Y = 0. 0 32 2 7C +0. 0 0 1 2 8, r = 0 .9999, n = 7. The absolute recoveries of high, medium and low concentrations of this method ranged from 73.4% to 80.5%. The method recoveries ranged from 97.3% to 1.06%. RSDs were less than 4% and daytime RSDs were less than 8%. The pharmacokinetic parameters of etodolac were Tmax = 0.28h ± 0.13h; Cmax = 69mg · L-1 ± 5mg · L-1; T 1/2 = 1.69h ± 2.lh; AUC = 2 31 4 mg · h · L -1 ± 32 8 mg · h · L -1. Conclusion: The method is fast, sensitive, accurate and reproducible. It is suitable for the determination of plasma concentration of etodolac and pharmacokinetics.