El-Yazbi Fawzy A, Amin Omayma A, El-Kimary Eman I, Khamis Essam F, Younis Sameh E, Elkhatib Mohammed Aw, El-Yazbi Ahmed F
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, El-Messalah, Alexandria 21521, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, 21311, Egypt.
Bioanalysis. 2019 Jan;11(1):41-54. doi: 10.4155/bio-2018-0219. Epub 2018 Nov 26.
To develop a simple HPLC-DAD method for simultaneous determination of febuxostat (FEB) and diclofenac (DIC) in biological samples to assess pharmacokinetic outcomes of their coadministration. Methodology & results: Sample preparation was performed by liquid-liquid extraction. Drugs analysis was done on C18 column using methanol-formic acid pH 2.1 (76:24, v/v) as mobile phase and time-programmed UV detection. Lower limits of quantitation for FEB and DIC were 10 and 20 ng/ml, respectively. Baseline pharmacokinetics were similar to published data on either drug alone. Coadministration led to more than twofold increase in FEB C and AUC together with a reduced hepatic uptake in rats.
DIC interfered with initial distribution and terminal clearance of FEB potentially due to reduced FEB hepatic uptake.
开发一种简单的高效液相色谱 - 二极管阵列检测法(HPLC - DAD),用于同时测定生物样品中的非布司他(FEB)和双氯芬酸(DIC),以评估它们联合给药后的药代动力学结果。方法与结果:采用液 - 液萃取进行样品制备。在C18柱上进行药物分析,以甲醇 - 甲酸pH 2.1(76:24,v/v)作为流动相,并采用时间程序紫外检测。FEB和DIC的定量下限分别为10和20 ng/ml。基线药代动力学与单独使用任一药物的已发表数据相似。联合给药导致大鼠体内FEB的血药浓度(C)和药时曲线下面积(AUC)增加两倍以上,同时肝脏摄取减少。
DIC可能由于FEB肝脏摄取减少而干扰了FEB的初始分布和终末清除。