Critical comparison of MS and immunoassays for the bioanalysis of therapeutic antibodies.

Therapeutic antibody assessment in biofluids requires fit-for-purpose bioanalytical methods. The reference is the immunoassay, the accuracy of which may be compromised by interference by endogenous components. Here, we report the inherent analytical problems posed by immunoassays and propose an alternative based on LC-MS that should be readily applicable to the analysis of therapeutic antibodies in biological fluids. We review problems linked to assay sensitivity, the choice of the assay format involving either immunodetection or MS, and strategies in the assessment of bound versus free forms.