Spectrophotometric and Titrimetric Assay of Flutamide in Pharmaceuticals

Resumo

Three methods, two spectrophotometric and one titrimetric, which are simple, easy to perform and cost-effective, are presented for the determination of flutamide, an anti-cancer drug. In the first spectrophotometric method (method A), absorbance of flutamide solution in methanol was measured at 290 nm. Measurement of absorbance of reduced flutamide (RFAD) in HCl at 245 nm serves as the basis of the second spectrophotometric method (method B). RFAD, in strong HCl medium was titrated vs standard sodium nitrite, determining the end-point potentiometrically (method C). Experimental variables influencing assays were studied and optimized. Beer’s law was obeyed over concentration ranges: 2.5–25.0 and 1.0–9.0 μg/mL for method A and method B, respectively, with molar absorptivity values of 1.0 × 10⁴ and 2.4 × 10⁴ L/(mol cm). Calculated limits of detection and quantification were 0.18 and 0.54 μg/mL (method A) and 0.16 and 0.18 μg/mL (method B). Titration reaction followed a 1: 1 stoichiometry and the method is applicable to 4‒30 mg RFAD. Repeatability, reproducibility and accuracy of the methods were satisfactory. The methods were also validated for selectivity, robustness and ruggedness. The developed methods were applied to the determination of active ingredient in tablets, and the results agreed well with the label claim and those of a reference method. Accuracy was also assessed by recovery test via standard–addition procedure. The drug was subjected to different stress conditions, such as acid and base hydrolysis, oxidation and thermolysis and analyzed subsequently by method A, as a part of stress testing. Results indicated that the drug is slightly vulnerable to all stress-conditions studied.