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Overcoming Electrochemiluminescence Immunoassay (ECLIA) Limitations: Conformation-Independent Quantitation of a Therapeutic Antibody by LC-MS/MS.

Created on 18 Aug 2026

Authors

Claudia Gaither, Robert Popp, Pradyumn Maheshwari, Mauricio Lemus, Julie Laurin, Mario Filion, Christoph H Borchers

Published in

Analytical chemistry. Volume 98. Issue 32. Pages 23440-23449. Aug 18, 2026.

Abstract

Monoclonal antibody therapies have transformed cancer treatment by enabling targeted intervention even in advanced disease stages. However, reliable monitoring of circulating therapeutic antibody levels is critical to ensuring efficacy and patient safety. This study investigates the limitations of an electrochemiluminescence immunoassay (ECLIA) in quantifying a therapeutic immunoglobulin G2 (IgG2) antibody, known to undergo conformational changes in vivo. We observed that the ECLIA failed to reflect increasing antibody concentrations in patient plasma, instead producing a plateau effect. This discrepancy was attributed to the ECLIA's reliance on the intact structural conformation of the antibody, which may be altered during circulation. In contrast, a mass spectrometry (MS)-based approach successfully quantified the accumulating antibody levels over time, independent of conformational state. These findings highlight the need for alternative quantitation strategies in clinical settings, particularly when structural heterogeneity may compromise the ECLIA performance. Mass spectrometry provides a robust and reliable option for monitoring therapeutic antibodies under these conditions.

PMID:
42610927
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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