Enhancing the Sustainability of Eco-Friendly Potentiometric Ion-Selective Electrodes for Stability-Indicating Measurement of Ethamsylate: Application in Bulk and Pharmaceutical Formulations

Abstract Background Through the use of sustainable and green chemistry concepts, scientists need to decrease waste, conserve energy, and develop safe substitutes for hazardous compounds, all for protecting and benefiting society and the environment. Objective Four novel eco-friendly ion selective electrodes (ISE) were generated to determine Ethamsylate (ETM) in bulk powder and different pharmaceutical formulations. The present electrodes were fabricated to clearly distinguish ETM from a variety of inorganic, organic ions, sugars, some common drug excipients and the degradation product, hydroquinone (HQ) of ETM, and thus used for stability-indicating methods. Methods The electrodes fabrication was based on 2-nitrophenyl octyl ether (NPOE) that was employed as a plasticizer in electrodes 1, 2, and 3 within a polymeric matrix of polyvinyl chloride (PVC) except for electrode 4, in which dibutyl sebacate was used as a plasticizer. Electrodes 1 and 2 were fabricated using tetradodecylammonium bromide as an anionic exchanger, adding 4-sulfocalix-8-arene as an ionophore only to electrode 2 and preparing electrode 1 without incorporation of an ionophore. The fabrication of electrodes 3 and 4 was based on ethamsylate–tetraphenylborate (ETM–TPB) as an ion-association complex in a PVC matrix. The environmental sustainability was assessed using the green analytical procedure index (GAPI), and analytical greenness metric for sample preparation (AGREEprep). Results Electrodes 1 and 2 had linear dynamic ranges of 10−1–10−5 mol/L and 10−1–10−4 mol/L, respectively, with a Nernstian slope of 49.6 and 53.2 mV/decade, respectively. Electrodes 3 and 4 had linear dynamic ranges of 10−1–10−4 mol/L, with a Nernstian slope of 43.9 and 40.2 mV/decade, respectively. Conclusion The electrodes' selectivity coefficients showed good selectivity for ETM. The utility of 4-sulfocalix-8-arene as an ionophore had a significant influence on increasing the membrane sensitivity and selectivity of electrode 2 compared to other electrodes. Highlights Four novel eco-friendly ISEs were used for determination of ETM in bulk powder and different pharmaceutical formulations. Different experimental parameters were performed to optimize the determination conditions such as solvent mediators, dynamic response time, effect of pH, and temperature. Stability-indicating measurement of ETM in the presence of its degradate HQ and co-formulated drug tranexamic acid. Using new ecological assessment tools to determine whiteness and greenness profiles.