Accuracy: a potential quandary in regulated bioanalysis of ‘endogenous’ analytes

The impetus for this commentary stems from recent interactions our laboratory has had with regulators reviewing drug applications and conducting on-site laboratory inspections involving submitted bioanalytical data for ‘endogenous’ analytes in both PD and PK situations. My intent is to provide some clarity on accuracy-related expectations, as we currently perceive them, for regulated bioanalysis of ‘endogenous’ analytes. The primary focus is on methods using LC–MS technology, but much of the discussion can be applied to ligand-binding assays (LBAs). Bioanalysis of endogenous compounds is complicated by multiple challenges including the availability and appropriateness of reference standard materials, confirming assay specificity and...