The increasing complexity of large molecule therapeutics has driven the need for additional approaches to quantitation in regulated bioanalysis where challenges with traditional ligand binding assays (LBA) are encountered for PK assay establishment. Hybrid immunoaffinity/mass spectrometry (IA/MS) techniques have been able to provide solutions such as improved selectivity, sensitivity, and the ability to multiplex measurements. This combination of techniques offers the advantages of specific antibody-antigen interactions together with the selectivity provided by the multiple dimensions of separation with liquid chromatography and mass spectrometry (LC−MS).