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In the past decade, LC‐MS‐based metabolomic/metabonomic profiling has become a major analytical focus for biomarker research. Chromatographic resolution is continually improving with the development of more advanced separation platforms based on smaller particle sizes, new types of stationary phase and miniaturized systems allowing the profiling of biological samples for metabolites in ways that were simply not possible before. Chromatographic advances, combined with increased mass resolution instruments that provide sub‐2 ppm mass accuracy and high sensitivity, have greatly facilitated the detection and identification of potential biomarkers. In this chapter, the most common LC(‐MS) methods utilized in metabolic analyses are presented, with emphasis on novel high‐efficiency and high‐throughput analyses and their suitability for metabolic analyses. Guidelines for the selection of the appropriate method for different applications are given, with emphasis on the use of LC‐MS.

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