Interference from anti-drug antibodies on the quantification of insulin: a comparison of an LC-MS/MS assay and immunoassays.

This study aims to compare the anti-drug antibody (ADA) interference in four pharmacokinetic (PK) assays across different platforms (AlphaLISA, Gyrolab, LC-MS/MS) and to devise a strategy for ADA interference mitigation to improve the accuracy of measured drug in total PK assays. Spiked test samples, created to achieve different ADA concentrations in human serum also containing an insulin analogue, were analyzed alongside pooled clinical samples using four assays. Interference was observed in all platforms. A novel approach using the Gyrolab mixing CD, including acid dissociation in the PK assay, significantly reduced interference and thereby improved relative error from >99% to ≤20% yielding measurements well within the acceptance criteria. Clinical sample results reinforced findings from the test samples.