A simple, efficient, and low-cost visible spectrophotometric method was developed for the determination of ephedrine hydrochloride with bromanil charge-transfer complexation using an alkaline medium. A stable yellow-colored species was obtained with a maximum absorption at 396 nm when the reaction was performed. The face-centered central composite design with response surface methodology enabled local optimization of the analytical response yielding a numerical optimum at 2.25 mL of 0.2% bromanil, 0.287 mL of 0.05 M NaOH and a reaction time of 39.21 min. For practical analytical application, these values were rounded to 2.25 mL of bromanil, 0.30 mL of NaOH, and 40 min. A confirmatory experiment, performed under the rounded conditions, yielded a mean absorbance of 0.4657 ± 0.0015 (RSD = 0.33%), supporting the suitability of the selected operating region for routine determination. Under the optimized multivariate conditions, Beer-Lambert's law was obeyed over the concentration range of 35–70 μg mL −1 , with a correlation coefficient of 0.9991, a detection limit of 3.1728 μg mL −1 , and a quantification limit of 9.61 μg mL −1 . The method showed acceptable intra-day and inter-day precision and was successfully applied to tested commercial injectable preparations, giving recoveries in the range of 97.37–98.49% with low RSD values. Further, stoichiometric and association studies indicate a drug-reagent ratio of 1:2 and a negative Gibbs free energy value (−23.1 kJ mol −1 ) but analysis by FTIR, DFT and TD-DFT supported the donor–acceptor form of the formed species. Such data indicate the method is applicable to routine determination of ephedrine hydrochloride, especially since it integrates practical simplicity, acceptable precision, and clear experimental conditions for routine analysis.
Zeadan et al. (Fri,) studied this question.