Eco‐Friendly Spectrophotometric Methods for Resolving the Spectral Inference of Benzalkonium Chloride During Alcaftadine and Ketorolac Tromethamine Quantification

Abstract

ABSTRACT The pharmaceutical industry has recently introduced a new combination of eye drop containing alcaftadine (ALF) and ketorolac tromethamine (KTC) utilized in managing allergic conjunctivitis. This new formulation elevates the necessity for developing sensitive, reliable, rapid and simple spectrophotometric methods to accurately quantify ALF and KTC in their dosage form with full consideration of its preservative benzalkonium chloride. In this study, three simple green spectrophotometric methods were developed to simultaneously determine ALF, KTC, and benzalkonium chloride in their ternary combinations without requiring preliminary separation steps. The expected methods employed unique spectral properties of the mixture including the extension of KTC's spectrum beyond that of ALF. The suggested methods were direct spectrophotometric, absorbance resolution, and factorized zero‐order methods. The proposed methods were assessed for validity in accordance with ICH guidelines and were determined to be linear within concentration ranges of 1.0–14.0 µg/mL for ALF and 3.0–30.0 µg/mL for KTC. A statistical comparison between the developed methods versus the reported and official methods revealed lack of any difference in terms of accuracy and precision. The work was also considered a successful attempt to stick to Green Analytical Chemistry principles and preserve our environment via using water as the main solvent. This was reflected by the highest greenness score of the proposed methods upon adopting state‐of‐the art assessment metric tools including Complementary Green Analytical Procedure Index (ComplexGAPI) and analytical GREEnness (AGREE). Considering these benefits, our developed methods were demonstrated to be green, sensitive, and accurate making it suitable for routine drug analysis.