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

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%.

In silico studies and in vitro microsomal metabolism of potent MetAP2 inhibitor and in vivo tumor suppressor for prostate cancer: A thioether-triazole hybrid

“…There are limited data available on HP-TLC and microsomal metabolism studies in the literature. This study is the first representative on this field in terms of HP-TLC usage in in vitro microsomal metabolism studies (41).…”

Optimization of Electrochemical Sensitivity in Anticancer Drug Quantification through ZnS@CNS Nanosheets: Synthesis via Accelerated Sonochemical Methodology

“…All electrochemical methods are based on the interaction of electrical energy and matter. The detection of flutamide has been generally done by traditional method of analysis, such as high performance thin-layer liquid chromatography (HPLC) [11] , mass spectrophotometry [1] , fluorescence quenching, spectrofluorimetric determination, first flow-injection method, reverse phase high performance liquid chromatography (RP-HPLC) and electrochemical methods [12] . As these methods have complex procedures, expensive instrumentation, their poor repeatability, limited to some materials and the necessary of skillful handling make them more vulnerable in terms of practical uses.…”

Determination of flutamide toward a real-time electrochemical sensor based on ultrathin reduced graphene oxide-covered MoW-P

“…The current methods used for monitoring FLT levels are electron spray ionization mass spectrometry (ESI-MS), 11 surface-enhanced Raman spectroscopy (SERS), 12 first injection (FI), 13 spectrofluorometry, 14 fluorescent sensors, 15 and high-performance liquid chromatography with photodiode-array detection and high-performance thin-layer chromatography (HPLC-DAD and HPTLC). 16 However, these methods have certain challenges such as being time-consuming and the need for an expert technician for the monitoring of FLT. The electrochemical detection method is the most precise among the various bio-interferents and is portable for on-site detection, as compared to other methods.…”