LC-MS/MS of large molecules in a regulated bioanalytical environment - which acceptance criteria to apply? "The current thinking from the EBF Topic Team is to start with a conservative approach when defining acceptance criteria and not to propose acceptance criteria that are still too demanding for the technology/analytical approach…"

Analysis of large molecules has become the talk of the day in the bioanalytical community. The increasing importance of peptides and proteins as therapeutic agents, together with the enormous possibilities offered by new MS-based technology, has opened a new world for the bioanalytical scientist. The European Bioanalysis Forum (EBF) has been following these new developments closely and have dedicated a Topic Team (TT) to discuss and share experiences on the bioanalysis of large molecules with LC–MS-based technologies. In this Editorial, the EBF wants to share their perspective on how to i ntegrate LC–MS of peptides and proteins in regulated bioanalysis. With larger molecules, that is, peptides, proteins and oligonucleotides, becoming increasingly important as therapeutic agents in the future, the scientific community is building their experience in analyzing these molecules within the framework of regulated bioanalysis. Traditionally, these types of molecules are analyzed using ligand-binding assays (LBA) and to date LBA remains the working horse, especially for proteins. However, a lot of progress has been made by the MS/TOF instrument vendors to improve the performance of these systems. And with success: the mass ranges are increasing and overall sensitivity, especially in the higher mass ranges, has improved tremendously. At the same time, advances in software and IT hardware have also enabled faster scanning and more flexible approaches to data mining. Another feature of MS-based assays is their selectivity. As a consequence, bioanalytical approaches based on MS for peptide and protein analysis are gaining increased interest [1–3].