RP-HPLC法测定大鼠血浆中萘哌地尔羟基代谢物浓度及药代动力学

RP-HPLC determination of concentration of metabolite of naftopidil in rat plasma and pharmacokinetics

目的:建立 RP-HPLC 法测定萘哌地尔羟基代谢物 RS-1-[4-(2-羟苯基)-1-哌嗪基]-3-(1-萘氧基)-2-丙醇(BWJ)在大鼠血浆的药物浓度及药代动力学,为此化合物的进一步开发提供依据。方法:以 Kromasil C_(18)柱(150mm×4.6mm 5μm)分离,萘哌地尔(NAF)为内标,流动相为甲醇-乙腈-磷酸盐缓冲液,检测波长为235nm。结果:BWJ 保留时间为10.3min,血药浓度在0.012～3.6mg·L^(-1)范围内线性关系良好,绝对回收率为72.0%～86.8%。大鼠十二指肠给予20mg·kg^(-1)后,药代动力学过程符合二室开放模型,t_(1/2α)、t_(1/2β)分别为(0.426±0.116)h,(2.69±0.222)h。结论:BWJ 吸收迅速,分布广泛,胆汁、尿、粪便中排泄量少,蛋白结合率高。

Objective： To establish a method for determining the concentration of RS - 1 - [ 4 - （ 2 - hydroxypbenyl） - 1 - piperazinyl ] - 3 - （ 1 - naphthoxy） - 2 - propanol （ BWJ ） metabolite of naftopidil in rat plasm and to study the pharmacokinetic profile of BWJ in rats and to provide pharmacokinetic data for BWJ＇ s further exploitation. Methods： A stainless steel column packed with C18 （Kromasil, 150 mm × 4. 6 mm 5 μm） was used, naftopidil （NAF） was chosen as the internal standard. The mobile phase was a mixture of methanol, acetonitrile and phosphate buffer and the detective wavelength is at 235 nm. Results：The retention time of BWJ was 10. 3 min. A good linear relationship of plasma concentration between 0. 012 -3.6 mg·L^-1 was observed. The mean absolute recovery was 72. 0% -86. 8%. The concentration - time curve of BWJ in rats conforms to two - compartment open model after administrated 20 mg ·kg^-1 to rats by duodenum. The t1/2α and t1/2β were（0. 426 ±0. 116）h, （2. 69 ±0. 222）h respectively. Condusion：BWJ is quickly absorbed from intestinal tract and distributed into tissues widely. It is excreted little in the bile, urine and feces but has a high protein -binding rate.