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作 者:钟皎[1] 柳晓泉[1] 王永升[1] 赵小平[1] 陈燕 王广基[1]
机构地区:[1]中国药科大学药物代谢与动力学研究中心,南京210009
出 处:《中国药科大学学报》2006年第3期238-241,共4页Journal of China Pharmaceutical University
基 金:国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A);江苏省药物代谢动力学重点实验室资助项目(No.BM2001201)~~
摘 要:目的:建立同时测定大鼠尿液中盐酸雷诺嗪及其代谢物的方法,用于研究其在大鼠体内的代谢。方法:在雌雄大鼠的尿液样品中加入内标甲巯咪唑,用0.1mol/L Na2CO3碱化后乙醚提取,取上清水浴挥干,流动相100μL溶解,取20止进行HPLC测定。色谱柱为汉邦Lichrospher C18柱(250mm×4.6mmID,5μm),采用梯度洗脱,流动相A:1mmol/L醋酸铵水溶液(用醋酸调节pH值至4.3);B:甲醇,流速1.0mL/min,检测波长271nm。结果:盐酸雷诺嗪线性范围为6.25~400μg/mL,方法回收率在98.5%-101.0%之间,日内和日间的精密度均小于9.3%。结论:本方法成功地应用于盐酸雷诺嗪在大鼠体内的代谢的性别差异性研究。Aim:To develop RP-HPLC method for simultaneous assay of ranolazine and its metabolites in rat urine and study gender-related metabolism in rats. Methods: Taken methimazole as the internal standard, the samples were alkalized with 0.1 mol/L Na2CO3 and extracted with diethyl ether. The upper layer was dried in water-bath and the residue was then reconstituted with 100 μL of the mobile phase and 20 μL were taken for HPLC use. Chromatography was performed on a Lichrospher C18 column (250 mm×4.6 mm ID, 5 μm), using the mobile phase which consisted of methanol and 1 mmol/L ammonium acetate (pH 4.3) and was operated in the mode of gradient elution with a flow rate of 1.0 mL/min. The eluent was monitored at the wavelength of 271 nm. Results: Calibration curves were linear over the concentration range of 6.25 -400 μg/mL. The intra-assay and inter-assay variability values were less than 9.3%. The extraction recovery of ranolazine from urine was in the range of 98.5% - 101.0%. Concluson: The established HPLC method is simple, accurate, sensitive and applicable for the study of geneder-related ranolazine metabolism.
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