A simple, fast, inexpensive and sensitive method has been proposed to screen and optimize experimental factors that effecting the determination of phenylephrine hydrochloride (PHE.HCl) in pure and pharmaceutical formulations. The method is based on the development of brown-colored charge transfer (CT) complex with p-Bromanil (p-Br) in an alkaline medium (pH=9) with 1.07 min after heating at 80 °C. ‘Design of Experiments’ (DOE) employing ‘Central Composite Face Centered Design’ (CCF) and ‘Response Surface Methodology’ (RSM) were applied as an improvement to traditional ‘One Variable at Time’ (OVAT) approach to evaluate the effects of variations in selected factors (volume of 5×10-3 M p-Br, heating time, and temperature) on the formation of the colored complex Y (absorbance) as graphical interpretation for robustness. The product was spectrophotometrically quantified at 395 nm. Beer’s law is obeyed in the concentration range of 5-20 μg. mL−1 with detection limit of 0.4191 μg. mL−1 . The molar absorptivity and Sandell’s sensitivity were found to be 6.07×103 L.mol−1 .cm−1 and 0.03356 μg.cm−2 respectively and the resulting color was stable for more than 1h. Applications of the recommended method to (PHE.HCl) pharmaceutical formulations was achieved with regard to accuracy and precision.
