反相-高效液相色谱法测定奥卡西平活性代谢物及其在健康人体的药代动力学特征

Determination of active metabolite of oxcarbazepine by RP-HPLC and study of its pharmacokinetics in Chinese healthy volunteers

目的建立测定奥卡西平活性代谢物的高效液相色谱法并进行药代动力学研究。方法10名健康志愿者单剂量口服奥卡西平300mg;血浆样品经液-液萃取,用高效液相色谱法检测奥卡西平10-单羟基代谢物(MHD)。用3P87程序进行数据处理。结果此方法适于血浆MHD浓度的检测。单剂量口服奥卡西平后,MHD的血浆浓度符合一级吸收的一室模型;其主要药代动力学参数为:tmax=(4.10±0.79)h,Cmax=(4.64±0.53)mg·L-1,t1/2ke=(15.05±2.32)h,AUC0-48=(112.97±14.25)mg·h·L-1。结论该法能高效、灵敏、准确地测定血浆中MHD。

Objective To determine the concentration of active metabolite of oxcarbazepine in human plasma and investigate its pharmacokinetics in Chinese healthy volunteers. Methods A single 300 mg dose of oxcarbazepine was performed in Chinese healthy male volunteers. Plasma samples were processed by liquid-liquid extraction and active monohydroxy metabolite (MHD), the active metabolite of oxcarbazepine, in plasma were determined by high performance liquid chromatography. Data were analyzed by a 3P87 program on a Legend computer. Results The method was utilized to determine the plasma concentration of MHD. Plasma concentration curve of MHD in single oral administration of oxcarbazepine conformed to one compartment model of the first order absorption. The major parameters of MHD were: t (max)=(4.10±0.79) h, C (max)=(4.64±0.53) mg·L^(-1), t (1/2 ke)=(15.04±2.32) h, AUC (0-48)=(112.96±14.25) mg·L^(-1)·h. Conclusion The method described in this report was of high sensitivity and selectivity for accurate determination of the plasma concentration of MHD in human. The pharmacokinetic results showed that it exhibited first order kinetic characteristics.