The construction and performance of plastic membrane (PME) oxytetracycline hydrochloride (OTC)-selective electrodes, based on three types of ion-pairs, OTC-tetraphenylborate (TPB), OTC-phosphotungstate (PT) and OTC-silicotungstate (SiT), as the electroactive substance in a plasticized PVC membrane with dibutylphthalate (DBP), were described. Furthermore, internal solid contact sensors (ISCS) OTC-selective sensors, based on a conducting polypyrrole (PPy) film immobilized on a platinum or glassy carbon electrode surface casted by a plasticized PVC membrane were constructed and evaluated. A novel optimization methodology in a numerical expression, comprehensive quality index (CQI) for a sensor, was used to optimize the composition of the membrane in the preparation of PME and screen the parameter of electropolymerization in the preparation of ISCS. Several PMEs and ISCSs were fully characterized and evaluated. An ISCS (Pt/PPy/PVC (OTC-TPB)) showed an excellent Nernstian response over the linear concentration range of 4.0 x 10(-7)-5.0 x 10(-2) M with the slope of 60.6 mV per decade (at 25 degrees C). The limit of detection was 1.0 x 10(-7) M of OTC (0.03 ppm). The response time was <25 s. The sensor was successfully used for the analysis of OTC in pharmaceutical formulation by using direct potentiometry.