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

Abstract

Aim: 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. Materials & methods: 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. Results & conclusion: 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.