Liquid Chromatography-Mass Spectrometry (LC-MS) is an indispensable, hyphenated analytical technique that has profoundly influenced the areas of chemistry, life sciences, and medicine. By synergistically combining the high-resolution separation power of Liquid Chromatography (LC) with the unparalleled selectivity and sensitivity of Mass Spectrometry (MS), LC-MS enables the qualitative identification and precise quantitative analysis of complex mixtures. This review article highlights the fundamental principles of LC-MS, surveys recent advances in its instrumentation, and discusses its transformative applications across three critical domains like pharmaceutical analysis, environmental analysis, and clinical diagnostics. Recent technological advances, especially in Ultra-High-Performance Liquid Chromatography (UHPLC) and High-Resolution Accurate Mass (HRAM) analyzers such as the Orbitrap, have secured LC-MS/MS as a gold-standard technique that continues to drive innovation in drug discovery, environmental contaminant monitoring, and personalized medicine.
