While small synthetic molecules remain the mainstay of drug development, a new wave of complex, large-molecule protein biotherapeutics are on the horizon. For example, monoclonal antibodies (mAbs) are one of the fastest growing classes of pharmaceutical products. They play a major role in the treatment of a variety of conditions such as cancer, infectious diseases, allergies, inflammation, and auto-immune diseases. Although protein-based therapeutics today represents a $48 billion dollar market, albeit comprised of only 130 licensed drugs, market growth is forecasted to be $141 billion in 2017 with the anticipated addition of new biotherapeutics. With increasing emphasis on protein therapeutics, performance improvements are required in the bioanalytical techniques used to support toxicokinetic, pharmacokinetic, and bioavailability data. Toward that end, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is being implemented with greater frequency for the determination of protein therapeutics in biological matrices. Why? In contrast to the limited dynamic range of many ligand binding assays (LBAs) and associated issues of non-specific binding and cross-reactivity, LC-MS/MS provides excellent selectivity, accuracy and precision, sensitivity (reduced sample volume) and a wide dynamic range. Further, LC-MS/MS methods can be developed and validated within a relatively short period and offer the potential for high throughput, an additional benefit when compared to the time required for antibody production and LBA development.  — Jeff Plomley, Principal Scientist, Bioanalysis, Charles River Laboratories Montreal