Eco-friendly cucurbituril-based potentiometric sensors for selective quantification of ipratropium bromide in pharmaceuticals and human plasma

This work presents a novel and innovative approach for the quantification of ipratropium bromide (IPBr), a quaternary ammonium drug widely used in the management of asthma and chronic obstructive pulmonary disease (COPD). IPBr is administered via inhalation. Despite its localized action in the lung and reduced systemic side effects, accurate quantification of IPBr in pharmaceutical formulations and biological matrices remains critical, especially in scenarios of accidental ingestion. The proposed method utilizes cucurbituril as a selective molecular receptor-type ionophore in potentiometric-based ion-selective electrodes (ISEs), offering a green, portable, and cost-effective alternative to traditional analytical techniques. Cucurbituril's unique hydrophobic cavity and polar portals enable highly selective encapsulation of IPBr through host-guest chemistry, enhancing sensitivity and ensuring accurate detection in complex matrices such as pharmaceutical preparations and human plasma. Two sensor platforms were developed: a liquid-contact and a solid-contact electrode. The solid-contact electrode was fabricated by drop-casting the membrane components onto a graphene-modified glassy carbon electrode. The solid-contact design eliminates the limitations of liquid-contact systems, while improving mechanical stability and compatibility with miniaturized devices. Both sensors demonstrated excellent Nernstian responses (around 57 mV/decade), rapid response times of 5 s, wide linear ranges (1 × 10^-6-1 × 10^-2 M), and high selectivity against interfering substances. The method was successfully validated for IPBr quantification in Atrovent® inhalers and spiked human plasma, demonstrating recoveries of 98.10-100.08% without any interference from excipients or biological matrices. This study presents cucurbituril-based solid-contact sensors as reliable and environmentally friendly tools for therapeutic drug monitoring and pharmaceutical analysis. The method's sustainability was evaluated using the Analytical Eco-Scale, AGREE, and RGB models, confirming its sustainable performance. The developed sensors also contribute to several United Nations Sustainable Development Goals (UN-SDGs), including those related to health, clean water, sustainable production, and innovation.