Here, we proposed that the use of an HCP carrier proteome could enhance the acquisition of spectra from HCPs amidst a highly abundance therapeutic protein background to perform global HCP analysis. We provide proof of principle of this approach, which we term carrier proteome-HCP (CP-HCP) analysis, using a basic model of bovine serum albumin (BSA) as a therapeutic protein and BL21 expression strain E.coli as a host cell proteome. We observe that MS3 based methods do not alleviate interference in this model due to the high mock therapeutic background, so we added an interference detection channel to filter co-isolation interference-containing peptides. The approach also does not require any type of enrichment and can identify hundreds of E.coli peptides at small quantities amidst a high background protein.