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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 RP-HPLC method for the determination of nalipepilil hydroxy metabolite RS-1- [4- (2-hydroxyphenyl) -1-piperazinyl] -3- The drug concentration and pharmacokinetics of alcohol (BWJ) in rat plasma provided the basis for the further development of this compound. Methods: Naftopidil (NAF) was separated on a Kromasil C 18 column (150 mm × 4.6 mm 5 μm). The mobile phase consisted of methanol - acetonitrile - phosphate buffer and the detection wavelength was 235 nm. Results: The retention time of BWJ was 10.3 min and the linear range was 0.012 ~ 3.6 mg · L ~ (-1). The absolute recovery ranged from 72.0% to 86.8%. After administration of 20 mg · kg ~ (-1) in rat duodenum, the pharmacokinetics was in accordance with the two-compartment open model, and the values of t 1 / 2α and t 1 / 2β were 0.426 ± 0.116 h, (2.69 ± 0.222) h. Conclusion: BWJ is rapidly absorbed and widely distributed, with less excretion of bile, urine and feces and high protein binding rate.