Effectiveness and Safety of Herbal Decoctions for Functional Dyspepsia in Korean Medicine Clinics: A Multicenter Prospective Cohort Study Protocol.

Mass spectrometry (MS) and chromatography have become crucial pillars of biomedical studies. Their coupling, indeed, allows researchers to tackle problems that range from the structural elucidation of biomolecules to their absolute quantification in highly complex biological matrices. The sensitivity, selectivity and versatility of these platforms make them fundamental tools for understanding the molecular mechanisms of disease, for biomarker discovery, for the study of drug metabolism and for the advancement of precision medicine [,]. This Special Issue, entitled , collects eight contributions that exemplify the breadth of these approaches (). Despite the diversity of the fields addressed, the papers share a common denominator: chromatography and MS are employed as tools to answer concrete biological and clinical questions. The collection can be read along two complementary lines. On the one hand, these techniques act as measurement tools, often replacing established but less reliable methodologies; on the other hand, they act as discovery tools, capable of generating new knowledge on pathological mechanisms and of identifying molecular markers with diagnostic and prognostic value. Furthermore, the eight contributions fall into three thematic groups, namely methodological innovation, clinical bioanalysis, and biomarker discovery, each drawing on these two lines in different proportions. . Di Ianni and co-workers propose a liquid chromatography-high resolution mass spectrometry (LC-HRMS) approach for the characterization of antibody–drug conjugates (ADCs), a class of therapeutic proteins central to cancer therapy, in which a cytotoxic payload is delivered selectively to tumor cells by conjugation to a monoclonal antibody []. Monitoring the “active” drug-to-antibody ratio (DAR) in circulation is highly informative but analytically demanding []. Indeed, payload hydrolysis involves minimal mass shifts that targeted multiple reaction monitoring (MRM) methods may overlook and that even high-resolution analyzers struggle to resolve on the intact antibody. To address this, the authors combine two complementary full-scan MS strategies that exploit the cleavable nature of the linker to release the payload in the gas phase, reproducing the cleavage that would occur in the lysosome without requiring separate enzymatic or chemical pretreatment. In this manner the small modifications are directly detectable, so that the sites of hydrolysis can be localized and the active DAR refined in both in vitro stability and in vivo pharmacokinetic samples, showing how high resolution coupled to a targeted fragmentation strategy can discriminate what would remain invisible using only MS analyses.