LC/MS VERSUS IMMUNE-BASED BIOANALYTICAL METHODS IN QUANTITATION OF THERAPEUTIC BIOLOGICS IN BIOLOGICAL MATRICES

This chapter reviews the main characteristics of liquid chromatography/mass spectrometry (LC/MS) and ligand-binding assay (LBA) methods. If an LBA method for biotherapeutics quantification is well established, it usually provides sufficient sensitivity and selectivity and is considered the method of choice. The LC/MS method emerged as an alternative strategy for quantification of proteins of interest in complex biological matrices. Multiplexed capacity and selectivity are critical features determining the applicability of a bioanalytical method. Well-established LBA methods usually provide adequate sensitivity for quantification analysis of biotherapeutics in preclinical/clinical pharmacokinetic (PK)/pharmacodynamic (PD) study. LC/MS with high resolution analyzer has become a promising technology for characterization of antibody-drug conjugate (ADC) in the recent years. An affinity capture capillary LC coupled to quadrupole-time-of-flight (TOF) MS has been employed to analyze anti-MUC16 TDC, which obtained both in vitro and in vivo drug-to-antibody ratios (DARs) information.