tCation exchange chromatography (CEX) of therapeutic monoclonal antibodies is generally performedwith either salt gradient (MES buffer + NaCl) or using commercial pH gradient buffer. The goal ofthis study was to find out some alternative buffer systems for CEX separation of mAbs, which mayoffer alternative selectivity, while maintaining similar peak shapes. Among the new buffers that weretested, (N-morpholino)ethanesulfonic acid (MES) / 1,3-diamino-2-propanol (DAP), and citric acid / 2-(cyclohexylamino)ethanesulfonic acid (CHES) systems were particularly promising, especially whencombining them with a moderate salt gradient of NaCl. This two buffer system provides an equivalent orslightly better separation than the standard, mobile phases for therapeutic mAbs.It was also demonstrated that working with salt-mediated pH gradients, allows to extend the pos-sibilities in method development, since the concentration of salt in the mobile phase has a significantimpact on selectivity. Using HPLC modeling software (Drylab), it was possible to successfully developCEX methods for authentic mAb samples within only 6 h, by optimizing the gradient steepness and saltconcentration in the B eluent.