The use of therapeutic recombinant monoclonal antibodies (mAbs) has triggered concerns of misdiagnosis of a plasma cell dyscrasia in treated patients. The purpose of this study is to determine if infliximab (INF), adalimumab (ADA), eculizumab (ECU), vedolizumab (VEDO), and rituximab (RITU) are detected as monoclonal proteins by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Methods: Pooled normal sera were spiked with various concentrations (ranging from trough to peak) of INF, ADA, ECU, VEDO and RITU. The peak concentration for VEDO and RITU was also added to samples with known monoclonal gammopathies. All samples were analyzed by SPEP (Helena Laboratories) and IFE (Sebia); sera containing peak concentrations of mAbs were reflexed to electrospray-time-of-flight mass spectrometry (AbSciex Triple TOF 5600) for the intact light chain monoclonal immunoglobulin rapid accurate mass measurement (miRAMM). Results: For all mAbs tested, no quantifiable M-spikes were observed by SPEP at any concentration analyzed. Small. fraction abnormalities were noted on SPEP for VEDO at 300 mu g/mL and RITU at 400 mu g/mL, with identification of small IgG. proteins on IFE. Using miRAMM for peak samples, therapeutic mAbs light chain accurate masses were identified above the polyclonal background and were distinct from endogenous monoclonal gammopathies. Conclusions: MAbs should not be easily confounded with plasma cell dyscrasias in patients undergoing therapy except when a SPEP and IFE are performed within a couple of days from infusion (peak). In ambiguous cases the use of the miRAMM technology could precisely identify the therapeutic mAb distinct from any endogenous monoclonal protein.54 10851093