双氯芬酸依泊胺凝胶在大鼠体内的药动学

Pharmacokinetics of Diclofenac Epolamine Gel in Rats

建立了液相色谱-串联质谱法测定大鼠血浆中的双氯芬酸,并考察皮肤局部给予双氯芬酸依泊胺凝胶后大鼠体内的药动学特征。血浆样品用甲醇沉淀蛋白,以布洛芬为内标,采用ESI源负离子模式、多反应监测(MRM)进行定量分析。检测离子对为m/z 295.9→m/z 252.0(双氯芬酸)和m/z 205.1→m/z 161.2(布洛芬)。双氯芬酸在1～200 ng/ml浓度范围内线性关系良好,方法回收率为97.80%～104.4%,日内、日间RSD分别小于6.12%和7.51%。SD大鼠经皮给予0.3 g双氯芬酸依泊胺凝胶后,主要药动学参数分别为:cmax(79.90±29.8)ng/ml,AUC0→t(1 198±349)ng.ml-1.h,AUC0→(1 358±567)ng.ml-1.h,tmax(4.8±2.8)h,t1/2(9.208±4.60)h,MRT0→t(11.22±1.06)h。

A LC-MS/MS method was established for the determination of diclofenac in rat plasma. The pharmacokinetic characteristics of diclofenac epolamine gel in rats after dermal topical administration were also investigated. The analyte and internal standard （ibuprofen） were extracted from plasma by protein precipitation with methanol. A tandem mass spectrometric detection was conducted under negative ionization mode with an electrospray ionization （ESI） interface. A multiple reaction monitoring （MRM） mode was chosen for the detection of m/z 295.9→m/z 252.0 （diclofenac） and m/z 205.1→m/z 161.2 （ibuprofen）. The calibration curve was linear in the concentration range of 1 - 200 ng/ml. The method recoveries were 97.80% - 104.4%. The intra- and inter-day RSDs were less than 6.12% and 7.51%, respectively. After applied 0.3 g diclofenac epolamine gel to skin of SD rats, the main pharmacokinetic parameters were as follows： Cmax （79.90±29.8） ng/ml, AUC0→t （1 198±349） ng·ml^-1·h, AUC0→∞ （1 358±567） ng·ml^-1·h, tmax （4.8±2.8） h, t1/2 （9.208±4.60） h, MRT0→t （11.22±1.06） h.