Recent advances in LC-MS/MS technology for improved selectivity and sensitivity

With an ever increasing fl ow of protein-based biopharmaceutical candidates entering the drug development funnel, reliable bioanalytical techniques are required to support quantitation in various biological fl uids in order to generate toxicokinetic, pharmacokinetic, and bioavailability data. Trends in the scientifi c literature clearly indicate that the coupling of liquid chromatography with tandem mass spectrometry (LC-MS/MS) is replacing traditional ligand binding assays due to improved selectivity and linear dynamic range, and that the mainstream MS approach for quantitation relies upon targeted proteomics techniques involving internal standardization, proteolytic digestion, surrogate peptide selection, peptide and/or protein purifi cation, LC separation and MS/MS detection. This review focuses primarily on recently reported advancements in MS workfl ows that have resulted in improved sensitivity through the eff ective elimination of interference from matrix components. Further, case studies are presented illustrating advantages of an immunocapture pre-digestion approach when LC-MS/MS alone fails to provide suitable required assay performance.