Recent advancements in high-resolution ion mobility spectrometry-mass spectrometry (IMS-MS) have enabled the separation of isotopologues and isotopomers based on their mass distribution-based isotopic shifts (i.e., changes in center of mass and moments of inertia). To better understand the fundamental nature of these isotopic shifts, we investigated whether they were additive in nature by introducing varying isotopic substitutions (e.g., 13C, 2H/D, and 81Br) through either hydrogen deuterium exchange or permethylation. From there, we measured the relative arrival times between light and heavy isotopologues with high-resolution cyclic ion mobility separations. Globally, we observed that the isotopic shifts were approximately additive in nature regardless of the molecule system or specific isomer studied. Furthermore, we discovered that additivity occurs in the isotopic shifts irrespective of the absolute shift, potentially indicating this observation may be more global in nature. We believe that our findings will serve to better understand the fundamental nature of mass distribution-based isotopic shifts and will inform theoretical ion mobility calculations in the future.