We used TMT labelling to set up different experiment channels containing mixtures of the host cell carrier proteome (E coli) and mock biotherapeutic (BSA), to compare with interference detection channel to model and filter interference, a phenomenon where host cell proteins (HCPs) co-elute with high-background biotherapeutic during LC-MS monitoring of QC during biomanufacture of biopharmaceuticals. Our work overcomes limitations of ELISA and pre-tryptic digest procedures to produce a reproducible method using TMT labels to identify and quantify a range of HCPs in one experiment.