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一种用于同时测定生物样品中非布司他和双氯芬酸的新型高效液相色谱-二极管阵列检测法:药代动力学结果

A novel HPLC-DAD method for simultaneous determination of febuxostat and diclofenac in biological samples: pharmacokinetic outcomes.

作者信息

El-Yazbi Fawzy A, Amin Omayma A, El-Kimary Eman I, Khamis Essam F, Younis Sameh E, Elkhatib Mohammed Aw, El-Yazbi Ahmed F

机构信息

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.

出版信息

Bioanalysis. 2019 Jan;11(1):41-54. doi: 10.4155/bio-2018-0219. Epub 2018 Nov 26.

DOI:10.4155/bio-2018-0219
PMID:30475064
Abstract

AIM

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.

CONCLUSION

DIC interfered with initial distribution and terminal clearance of FEB potentially due to reduced FEB hepatic uptake.

摘要

目的

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。

结论

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。

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