The sustainable and green chemistry principles enable scientists to protect and benefit the economy, people and the planet by finding creative and innovative ways to reduce waste, conserve energy, and discover replacements for hazardous substances. In this work, an environmentally friendly ion selective electrode (ISE) potentiometric method was developed for the determination of cinchocaine hydrochloride (CIN) in presence of its degradation products either in bulk powder or in its combined pharmaceutical formulation with betametahsone valerate. Two novel CIN-selective electrodes were fabricated and evaluated. The fabrication of electrodes was based on sodium tetrakis [3, 5-bis (trifluoromethyl) phenyl] borate as a cationic exchanger in a PVC matrix with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer and using 2-hydroxy propyl-β-cyclodextrin (2-HP β-CD) as an ionophore. A comparative study was conducted using two designed CIN-selective electrodes; a conventional liquid inner contact, sensor 1, and a glassy carbon solid contact electrode, sensor 2. Sensor 1 has a linear dynamic range of 3.0× 10− 5 mol L− 1 to 1.0× 10− 2 mol L− 1, with a Nernstian slope of 54.89 mV/decade and a detection limit of 5.01× 10− 6 mol/L. Sensor 2 shows linearity over the concentration range of 1.0× 10− 5 mol L− 1 to 1.0× 10− 2 mol L− 1, with a Nernstian slope of 57.01 mV/decade and a limit of detection of 2.51× 10− 6 mol L− 1 which is much improved as a result of diminishing ion fluxes in this solid contact ion-selective electrode. The present electrodes show clear selectivity for CIN from several inorganic, structurally related organic molecules, sugars, co-formulated drug, some common drug excipients and its degradation products. The results obtained by the proposed sensors were statistically analyzed and compared with those obtained by official method. No significant difference for either accuracy or precision was observed.