The focus of the present investigation was epitope mapping of a mouse monoclonal antibody to the receptor binding domain of two SARS-CoV-2 spike protein variants (Wild-Type and variant B.1.617.2). The experimental setup utilizing multiple controls allowed for validation of false positive binding on several levels, while still being easily implementable in the general MS laboratory. The primary equipment needed to implement this method in addition to a mass spectrometer is a pipetting robot e.g., Opentrons OT-2.