Materials with multiple principal elements (middle- and high-entropy materials), are used in emerging applications in various fields due to their unique properties, driven by configuration entropy. Improved understanding and experimental investigations of the impact of the entropy of mixing on the properties of these materials are of large practical interest. Here we show a simplified limited area calculation approach for assessing the entropy of mixing using a CoCuFeNi model nanoalloy. Based on our calculations we propose a new parametric entropy-based criterion, which defines critical scale parameter transition from the maximal entropy state to the entropy-depleted state of the system. The criterion could be used for generalized mechanistic assessment of the effect of the entropy of mixing on the characteristics of the materials with multiple principal elements and for the development and characterization of existing and new middle- and high-entropy materials with both simple single-, and more complex, multiple-sublattice structures.