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

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.

Keywords: alcaftadine; benzalkonium chloride; green chemistry; ketorolac tromethamine; spectrophotometry.

FIGURE 1

Chemical structures of (a) alcaftadine, (b) ketorolac tromethamine, and (c) benzalkonium chloride.

FIGURE 2

Zero order (D ⁰) absorption spectra of 10.0 µg/mL alcaftadine, 15.0 µg/mL ketorolac tromethamine, and 60.0 µg/mL benzalkonium chloride using water as solvent.

FIGURE 3

Zero order (D ⁰) absorption spectra of 10.0 µg/mL alcaftadine, 15.0 µg/mL ketorolac tromethamine, and 60.0 µg/mL benzalkonium chloride; showing the selected two wavelengths (λ ₁ = 234.0 nm and λ ₂ = 287.0 nm).

FIGURE 4

Spectral scheme illustrating the application of factorized zero‐order method on a mixture of 10.0 µg/mL alcaftadine and 10.0 µg/mL ketorolac tromethamine in presence of 60.0 µg/mL benzalkonium chloride.

FIGURE 5

Greenness profile evaluation of (a) the proposed, (b) reported spectrophotometric methods via ComplexGAPI as well as AGREE tools.