Analysis of protein drug targets and impurities via LCMS involves time consuming offline protein digestion and separation. Automated protein digestion systems have addressed concerns of irreproducibility and improved laboratory efficiency by reducing human interaction with the sample. Although peptide mapping and Immuno-MS workflows are well established for on-line digestion, more complicated, orthogonal analyses have yet to be explored. Protein digestion of analyte proteins can be performed with or without affinity pulldown (depletion) of target proteins to enhance recovery of impurity proteins. A configuration change allows separation and intact mass data of proteins to be acquired in addition to peptide data from the same sample by employing two parallel flow paths.