高效液相色谱法测定依托度酸及其在大鼠的药动学(英文)

High performance liquid chromatography method determination of etodolac and study of its pharmacokinetics in rats

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。

AIM: To establish HPLC method for the determination of etodolac and to study pharmacokinetics of etodolac in rats. METHODS: Etodolac and internal standard (oxaprozin) were analyzed on C 18 column with an acetonitrile : water: triethylamine (16∶84∶0.002) mobile phase at 1.0 mL·min -1 flow rate. The UV detector was set at 280 nm. Rats' blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, 12, 24, 48, 72 h after treatment of once 20 mg·kg -1 dose of etodolac and pharmacokinetic parameters were calculated. RESULTS: The retention time of etodolac and internal standard were 5.28 min and 6.80 min, respectively. The calibration curve was linear in the range of 1.0～100.0 mg·L -1 ( r = 0.9999, n = 7). The extraction recovery was between 73.4% and 80.5%, and the methodological recovery was between 97.3% and 106.0%. The intra day RSD and inter day RSD were less than 4% and 8%, respectively. The pharmacokinetic parameters of etodolac were 0.28 h± 0.13 h for T max ; 69 mg·L -1 ±5 mg·L -1 for C max ; 16.9 h±2.1 h for T 1/2; 2314 mg·h·L -1 ±328 mg·h·L -1 for AUC. CONCLUSION: This method is simple, sensitive, as well as rapid, and is suitable for application in pharmacokinetic study of etodolac.