From Complexity to Clarity: Expanding Metabolome Coverage With Innovative Analytical Strategies.

Metabolomics, a powerful discipline within systems biology, aims at comprehensive profiling of small molecules in biological samples. The challenges of biological sample complexity are addressed through innovative sample preparation methods, including solid-phase extraction and microextraction techniques, enhancing the detection and quantification of low-abundance metabolites. Advances in chromatographic separation, particularly liquid chromatography (LC) and gas chromatography (GC), coupled with high-resolution (HR) mass spectrometry (MS), have significantly improved the sensitivity, selectivity, and throughput of metabolomic studies. Cutting-edge techniques, such as ion-mobility mass spectrometry (IM-MS) and tandem MS (MS/MS), further expand the capacity for comprehensive metabolite profiling. These advanced analytical platforms each offer unique advantages for metabolomics, with continued technological improvements driving deeper insights into metabolic pathways and biomarker discovery. By providing a detailed overview of current trends and techniques, this review aims to offer valuable insights into the future of metabolomics in human health research and its translational potential in clinical settings. Toward the end, this review also highlights the biomedical applications of metabolomics, emphasizing its role in biomarker discovery, disease diagnostics, personalized medicine, and drug development.