:Metal-binding antibiotics are very attractive choices as cation selective ionophores. The ability of tetracycline (TC) antibiotics to bind to metal ions has obtained much attention. TCs exhibit the potentiometric performance changes for various cations dependant on several experiment conditions. In this report, we investigated the potentiometric performance changes of TC as the modification of TC's possible metal binding site. We found that the selectivity alter with the blocking main binding site of ionophores for cations. And, additionally it is possible to control the selectivity of sensors with chemical modification of ionophores.