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It is a problem to be solved that the experimental selectivity coefficients of ion selective electrodes (ISEs) depend on the activity.This paper studied the new method of determining selectivity coefficients.A mixed ion response equation,which was similar to Nicolsky-Eisenman (N-E) equation recommended by IUPAC,was proposed.The equation includes the practical response slope of ISEs to the primary ion and the interfering ion.The selectivity coefficient was defined by the equation instead of the N-E equation.The experimental part of the method is similar to that based on the N-E equation.The values of selectivity coefficients obtained with this method do not depend on the activity whether the electrodes exhibit the Nernst response or non-Nernst response.The feasibility of the new method is illustrated experimentally.