A comparative study was conducted using two designs of a roxatidine acetate (ROX)-selective electrode; a conventional liquid inner contact called electrode A and a graphite-coated solid contact called electrode B. The fabrication of electrodes was based on roxatidine-tetraphenylborate (ROX-TPB) as an ion-association complex in a PVC matrix using different plasticizers. Electrode A has a linear dynamic range of 2.2×10^-5 mol/L to 1.0×10^-2 mol/L, with a Nernstian slope of 54.7 mV/decade and a detection limit of 1.4×10^-6 mol/L. Electrode B shows linearity over the concentration range of 1.0×10^-6 mol/L to 1.0×10^-2 mol/L, with a Nernstian slope of 51.2 mV/decade and a limit of detection of 1.1×10^-7 mol/L which is remarkably improved as a result of diminishing ion fluxes in this solid contact, ion-selective electrode. The proposed sensors display useful analytical characteristics for the determination of ROX in bulk powder and its pharmaceutical formulation. The present electrodes show clear discrimination of ROX from several inorganic, organic ions, sugars, some common drug excipients and the degradation product (3-[3-(1-piperidinyl methyl) phenoxy] propyl amine) of ROX. Furthermore, the proposed electrodes were utilized for the determination of ROX in human plasma, where electrode B covers drug C_max which indicated its applicability to pharmacokinetic, bioavailability and bioequivalent studies. The results obtained by the proposed electrodes were statistically analyzed and compared with those obtained by a reported HPLC method. No significant difference for either accuracy or precision was observed.