Spectrophotometric Estimation of Flutamide in Pure and in Pharmaceutical Preparations

Three simple, rapid, precise, sensitive, and accurate visible spectrophotometric methods (A, B, and C) are described for the estimation of flutamide in both pure and pharmaceutical preparations. They are based on the diazotization of reduced flutamide (FA) with nitrous acid followed by coupling with acetyl acetone (method A), citrazinic acid (method B), and 8-hydroxyquinoline (method C) to form colored azo dyes, exhibiting absorption maxima at 410, 440 and 500？nm, for methods A, B, and C, respectively. Linear concentration range was of 0.5–12, 0.5–10, and 0.3–10？μg/mL for methods A, B, and C, respectively, and the corresponding molar absorptivity values are , , and ？L mol？1？cm？1. The correlation coefficients for FA are 0.9988, 0.9976, and 0.9975 for methods A, B, and C, respectively. All variables were optimized, and the results were statistically compared with those of a literature method by employing Student’s t-test and F-test. No interference was observed from common adjuvants normally added to the tablets. The relative standard deviations ( ) for FA in all the three methods in the tablets are always less than 3%. 1. Introduction Flutamide (FA), chemically known as 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide (Figure 1), is a potent nonsteroidal antiandrogen drug primarily used to treat prostatic cancer [1–3]. FA competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland thereby, and it inhibits the prostate cancer cells to grow. Flutamide has been largely replaced by a newer member of this class, bicalutamide, due to a better side-effect profile. Flutamide may also be used to treat excess androgen levels in women—especially those with polycystic ovarian syndrome (PCOS) [4]. This drug and its primary hydroxy metabolite decrease metabolism of C-19 steroids by the cytochrome P-450 system at the target cells in the secondary sex organ [5]. The official method for its determination is liquid chromatography reported in European Pharmacopoeia [6]. Figure 1: Structure of flutamide. Different analytical methods for the quantitative determination of FA in pure form, in pharmaceutical preparations and in biological fluids, including HPLC [7–9], electrochemical reduction [10], stripping voltammetry [11], spectrofluorometry [12], and spectrophotometry [13–15] have been reported. The reported chromatographic techniques [7–9] require expensive experimental setup and are not affordable in every laboratory for routine analysis. The stripping voltammetric technique [11]