Two novel potentiometric sensors are prepared, characterized and successfully used for static and continuous determination of ceftriaxone sodium (CRXN). Both sensors are based on the use of plasticized PVC matrix membranes incorporating tetradodecylmethyl ammonium bromide (TDMAB), ortridodecylmethyl ammonium chloride (TDMAC) ion-exchangers and used for quantitative determination of CRXN at concentration level down to 29 µM using both sensors with a good accuracy. Both sensors offer the advantages of fast response, reasonable selectivity, elimination of drug pre-treatment or separation steps, low cost and possible interfacings with computerized and automated systems. The use of plasticized membrane electrodes were used for continuous monitoring of CRXN offers the advantages of simple design, ease of construction and possible applications to small volumes of drug solutions with little manipulation and without pre-treatment. Both detectors display a wide dynamic measurement range of the drug under continuous mode of operation with a flow rate of 2.0 ml.min-1 and used for quantitative determination of CRXN. The developed sensors were utilized in static continuous modes successfully for the determination of CRXN in pure powders and in dosage forms. It is worth noting that the developed membrane electrodes exhibited good selectivity toward CRXN over other cephalosporins such as; cefradine, ceftazidime, cefadroxil, cefaclor and cefoperazone, as well as other additives found in the pharmaceutical preparations such as; glucose, fructose and maltose.