Potentiometric Analysis of Benzalkonium Chloride with 3D Printed Ion-Selective Membranes

Abstract

Benzalkonium (BA+) chloride is one of the most common preservatives used in prescription-based and over-the-counter eye drops. Knowing the concentration of BA+ in eye drops is important for both quality control (at the pharmaceutical preparation stage) and human health (ocular toxicity has been linked to BA+ use). This paper describes the design and fabrication of a benzalkonium-selective potentiometric sensor for the determination of BA+ in ophthalmic solutions. The sensor is composed of a 3D-printed ion-selective membrane (ISM) that selectively measures BA+ in the presence of potentially interfering ions routinely found in ophthalmic formulations (i.e., Mg2+, Ca2+, Na+ and K+). The 3D printed BA+-ion-selective electrodes (ISEs) produced a Nernstian response of 55 mV/Decade across a range of 1.0 mM to 31.0 μM BA+ along with an LOD of 8 μM, which covers the relevant concentration range found in ophthalmic solutions. The 3D printed BA+-ISEs proved to be highly stable with an average drift of 205 μV/hr. Successful measurement of BA+ in diluted ophthalmic solutions was completed from 100-500 μM. The mass production capability afforded by 3D-printing offers a unique and intriguing fabrication protocol for developing low-cost sensors which could be incorporated quickly and seamlessly by pharmaceutical companies or community-based pharmacies.