Factors affecting the performance of polyvinyl chloride (PVC) based ISE were recently the scope of study by several researchers; however, no enough data has related to the thickness of the PVC membrane to performance characteristics and sensitivity of sensors. The current work introduces an ecofriendly experimental approach to evaluate the effect of membrane composition including ion exchanger and plasticizer along with thickness on the performance of a PVC sensor for determination of a tocolytic selective beta(2) -agonist; ritodrine HCl (RTH), in presence of its active impurity, tyramine. Thirteen different PVC membranes were prepared by varying the content of ion exchanger types and amounts constructing different thickness to address their effect on their performance characteristics. A comparative study was held among the fabricated sensors for determination of RTH in pharmaceutical dosage form, and biological fluids including human plasma and urine. It was found that the thickness of liquid membrane electrodes had a remarkable effect on the sensitivity of PVC based ion-selective electrode. The proposed sensors proved acceptable selectivity for RTH against tyramine and common inorganic species. The proposed technique presents a green alternative to reported ones by saving cost, time and effort, and yielding of the minimum amount of wastes. (C) 2018 The Electrochemical Society.