Determination of flutamide and two major metabolites using HPLC-DAD and HPTLC methods.

Q1 Chemistry
Nada S Abdelwahab, Heba A H Elshemy, Nehal F Farid
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引用次数: 0

Abstract

Flutamide is a potential antineoplastic drug classified as an anti-androgen. It is a therapy for men with advanced prostate cancer, administered orally after which it undergoes extensively first pass metabolism in the liver with the production of several metabolites. These metabolites are predominantly excreted in urine. One of the important metabolites in plasma is 4-nitro-3-(trifluoromethyl)phenylamine (Flu-1), while the main metabolite in urine is 2-amino-5-nitro-4-(trifluoromethyl)phenol (Flu-3). In this work the two metabolites, Flu-1 and Flu-3, have been synthesized, and then structural confirmation has been carried out by HNMR analysis. Efforts were exerted to develop chromatographic methods for resolving Flutamide and its metabolites with the use of acceptable solvents without affecting the efficiency of the methods. The drug along with its metabolites were quantitatively analyzed in pure form, human urine, and plasma samples using two chromatographic methods, HPTLC and HPLC-DAD methods. FDA guidelines for bio-analytical method validation were followed and USP recommendations were used for analytical method validation. Interference from excipients has been tested by application of the methods to pharmaceutical tablets. No significant difference was found between the proposed methods and the official one when they were statistically compared at p value of 0.05%.

使用 HPLC-DAD 和 HPTLC 方法测定氟他胺和两种主要代谢物。
氟他胺是一种潜在的抗肿瘤药物,属于抗雄激素类药物。它是一种治疗晚期前列腺癌男性患者的药物,口服后会在肝脏中进行广泛的首过代谢,产生多种代谢物。这些代谢物主要通过尿液排出。血浆中的重要代谢物之一是 4-硝基-3-(三氟甲基)苯胺(Flu-1),而尿液中的主要代谢物是 2-氨基-5-硝基-4-(三氟甲基)苯酚(Flu-3)。本研究合成了 Flu-1 和 Flu-3 这两种代谢物,并通过 HNMR 分析进行了结构确认。在不影响方法效率的前提下,研究人员努力使用可接受的溶剂,开发用于分辨氟他胺及其代谢物的色谱方法。采用 HPTLC 和 HPLC-DAD 两种色谱法对纯品、人体尿液和血浆样品中的药物及其代谢物进行了定量分析。生物分析方法验证遵循 FDA 指南,分析方法验证采用 USP 建议。通过将这些方法应用于药片,测试了辅料的干扰。在 p 值为 0.05% 时,建议的方法与官方方法进行统计比较,未发现明显差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chemistry Central Journal
Chemistry Central Journal 化学-化学综合
CiteScore
4.40
自引率
0.00%
发文量
0
审稿时长
3.5 months
期刊介绍: BMC Chemistry is an open access, peer reviewed journal that considers all articles in the broad field of chemistry, including research on fundamental concepts, new developments and the application of chemical sciences to broad range of research fields, industry, and other disciplines. It provides an inclusive platform for the dissemination and discussion of chemistry to aid the advancement of all areas of research. Sections: -Analytical Chemistry -Organic Chemistry -Environmental and Energy Chemistry -Agricultural and Food Chemistry -Inorganic Chemistry -Medicinal Chemistry -Physical Chemistry -Materials and Macromolecular Chemistry -Green and Sustainable Chemistry
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