We tested here the ability of weak cation exchange (WCX) stationary phase to retain positively charged proteinaceous whilst negatively charged SDS molecules can be washed out from the capillary during on-line desalting. This novel chromatographic method named as online desalting of sodium dodecyl sulfate (online deSDS) satisfactorily allows for the first time the unforeseen straightforward LC-MS/MS analysis of SDS-containing samples without the requirement of any additional pre-processing step.