Electroanalysis of Benzalkonium Chloride in Ophthalmic Formulation by Boron-doped Diamond Electrode

Benzalkonium chloride (BAK) is a mixture of alkyl benzyl dimethyl ammonium chlorides, which is used primarily as a biocide, surfactant, preservative, and antimicrobial agent in the pharmaceutical industry, in particular in ophthalmologic and nasal solutions. However, BAK may cause harmful consequences on the eye structures of the anterior segment. Control of BAK identity and content is necessary by applying a sensitive detection method. This study unravels the use of a glassy carbon (GC) electrode and a pristine boron-doped diamond electrode (BDD) for the detection of four BAK homologs in a non-aqueous medium using square wave voltammetry (SWV). The BDD provided more reproducibility of the oxidation potential than GC with a correlation coefficient of 0.999. The irreversible oxidation peak was very broad and deconvoluted into 3 peaks corresponding to C₁₂, C₁₄, and combined C₁₆–C₁₈ to reflect their concentration ratio in the mixture. The method was then extended to the detection of the C₁₂ homolog in the ophthalmic formulations with a limit of detection (LOD) of 0.4 μg/mL. The estimated BAK levels in three ophthalmic formulations were in agreement with the specified values by the manufacturers. The results were validated by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection, confirming the presence of a single homolog (C₁₂) in the eye drops.