Spectrophotometric and theoretical studies on the determination of etilefrine hydrochloride in pharmaceutical formulations and biological samples

Purpose: To develop a simple and cost effective spectrophotometric method for the determination of etilefrine hydrochloride (ET) in pharmaceutical formulations and human plasma.Methods: The method is based on extraction of ET into chloroform as ion-pair complexes with bromocresol green (BCG) and methyl orange (MO) in acidic medium. The interaction of ET with BCG and MO reagents were investigated using B3LYP/6-31G(d) level of theory. The geometrical parameters of the interacting species and the ion pairs formed were characterized based on their frontier molecular orbitals, atomic charges, electrostatic potential map, as well as NBO analysis.Results: The colored species exhibited absorption maxima at 410 and 479 nm for the two systems in universal buffer of pH range (3.0 - 3.5), with molar absorptivity of 2.4 × 104 and 1.7 × 104 Lmol-1cm-1, for BCG and MO methods, respectively. The methods demonstrated good linearity with correlation coefficient ranging from 0.9987 – 0.9991 in the concentration ranges 0.5 – 16 and 2.0 – 18 μgmL-1 for BCG and MO methods, respectively. The composition ratio of the ion-association complexes was 1:1 in all cases as established by Job’s method. Sandell,s sensitivity, correlation coefficient, detection and quantification limits were also calculated. Molecular descriptors were obtained based on optimized structures of the molecules under investigation, by applying the B3LYP/6-31G(d) method, and used to interpret the mode of interaction between these molecules to form the investigated ion pairs.Conclusion: The proposed methods make use of simple reagents, which a basic analytical laboratory can afford. No interference was observed from common pharmaceutical excipients and additives. ETMO ion pair has a larger interaction energy (higher stability) than ET-BCG ion pair as inferred from their interaction energies.Keywords: Density functional theory, Etilefrine hydrochloride, Ion pair complex, Spectrophotometry, Bromocresol green, Methyl orange, Geometric analysi