The utility of mass spectrometry-(MS-) based proteomic platforms and their clinical applications have become an emerging field in proteomics in recent years. Owing to its selectivity and sensitivity, MS has become a key technological platform in proteomic research. Using this platform, a large number of potential biomarker candidates for specific diseases have been reported. However, due to lack of validation, none has been approved for use in clinical settings by the Food and Drug Administration (FDA). Successful candidate verification and validation will facilitate the development of potential biomarkers, leading to better strategies for disease diagnostics, prognostics, and treatment. With the recent new developments in mass spectrometers, high sensitivity, high resolution, and high mass accuracy can be achieved. This greatly enhances the capabilities of protein biomarker validation. In this paper, we describe and discuss recent developments and applications of targeted proteomics methods for biomarker validation. 1. Introduction Recently, advanced proteomics technology and instrumentations has allowed for the generation of more than a thousand candidate biomarkers from the profiling of complex biological samples. Most of these proteins were from under powered studies or pooled samples that had a large number of hypotheses being tested in similar conditions. Protein biomarkers have great potential to improve diagnosis, guide targeted therapy, and monitor therapeutic response across a wide range of diseases [1]. Mass spectrometry-based proteomics has become a powerful tool for biomarker discovery and validation in recent years [2–4]. However, to date, no protein biomarker identified using proteomics has been introduced into clinical use [5–9]. Although “omics” technologies have revolutionized the discovery of candidate biomarkers, several major technological limitations, including sensitivity, accuracy, and reproducibility, have hindered the application of proteomics as a platform for biomarker research. Discovery proteomics has enabled the identification of hundreds of biomarker candidates in many disease types, but the lack of well-established methods for validation of the biomarker candidates involving a large number of clinical samples is blamed for the low yield of clinically useful biomarkers [10–12]. The linkage between new technological platforms and the discovery of truly disease-related biomarkers needs to be established before moving candidate protein biomarkers toward clinical implementation. Recent advances in mass spectrometry and
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