Devices and methods for measuring a target ion concentration uses an electrode pair. The pair includes a working electrode and a reference electrode. The working and reference electrodes are ion-selective electrodes (ISEs). The reference ISE can include a sodium ISE. The ISE pair interacts with body fluids where a target ion concentration changes more than sodium ion concentration over time. Some ISE membranes of a pair vary essentially only in the ionophore. An ISE pair can determine the ratio of a target ion concentration to sodium ion concentration in vivo. Periodic measurement of sodium concentration in drawn blood can be used to calibrate an ISE pair and provide target ion concentration as an output. Or, a potassium/sodium ISE pair beneficially monitors potassium concentration changes over time in heart- or kidney-failure patients. Then, manual or automatic titration of a diuretic material can be implemented to maintain a desired potassium concentration.