Researchers from Université Claude Bernard Lyon’s Institut des Sciences Analytiques reported a targeted proteomics workflow to improve host-cell protein (HCP) monitoring across variable biomanufacturing matrices. The team identified that conventional retention-time scheduled MRM can fail due to multi-minute retention shifts across different drug substances and process intermediates. Their solution, scout-triggered MRM (st-MRM), uses predefined scout peptides to dynamically trigger groups of transitions during runs, improving transferability without re-optimizing for each sample type. The study reported robust absolute quantification across six orders of magnitude, including detection down to 2.9 parts per million in purified drug substance. For manufacturers and regulators expecting consistent HCP control, the approach provides a more resilient, targeted alternative to ELISA limitations by enabling protein-specific impurity characterization.