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

作　　者：陈修平[1] 龚其海[1] 袁牧[2] 谢笑龙[1] 陆远富[1] 吴芹[1] 黄彬[1] 杨丹莉[1] 石京山[1] 

机构地区：[1]遵义医学院药理学教研室,遵义563003 [2]贵州省-中国科学院天然产物化学重点实验室,贵阳550002

出　　处：《药物分析杂志》2006年第5期609-613,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(30060087);贵州省科技基金重点项目(计[2002(3014)])资助课题

摘　　要：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.

关 键 词：RS-1-[4-(2-羟苯基)-1-哌嗪基]-3-(1-萘氧基)-2-丙醇(BWJ) 萘哌地尔(NAF) 药代动力学 反相高 效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]