Monoclonal antibodies (mAbs) present analytical challenges due to their inherent heterogeneity and susceptibility to post translational modifications (PTMs) during production and storage. Monitoring of charge heterogeneity profiles by imaged capillary isoelectric focusing (icIEF) has been aided by the use of non-detergent sulfobetaines (NDSBs), particularly NDSB-211, to enhance protein solubility and stability. When used in a quality control laboratory setting, NDSB-211 has shown performance variability over time due to residual manufacturing impurities that impact the capillary isoelectric focusing separation. Dimethylformamide (DMF) was detected using 1H nuclear magnetic resonance (NMR) in several lots of NDSB-211 that simultaneously produced poor resolution of basic variants of a mAb on icIEF. A parallel spiking study using DMF at 1%–10% (v/v) on ¹HNMRand icIEF illustrates the interference in charge heterogeneity separation when a large amount of DMF is present in the NDSB-211 reagent. As DMF is not found on the NDSB-211 certificate of analysis from any vendor, more traditional additives for icIEF are suggested to limit the potential interference for analytical methods.