Novel materials and approaches for solid-phase (micro) extraction in LC-MS-based metabolomics

Metabolomics offers a unique approach to study biological systems. Liquid chromatography coupled to mass spectrometry serves as a powerful analytical tool to analyze complex mixtures of metabolites. However, successful metabolomic analysis relies on sample preparation. While untargeted analysis traditionally favors non-selective procedures like liquid-liquid extraction (LLE), these methods can compromise analytical performance due to limited analyte enrichment and potential matrix interferences. Solid-phase extraction (SPE) has emerged as a well-established and versatile technique for this purpose, offering advantages over other traditional methods like LLE. This review explores the applications of SPE and solid-phase microextraction (SPME) in LC-MS-based metabolomics. We discuss various modes of SPE, ranging from conventional flow-through cartridges and plates to approaches involving the dispersion of sorbent in a sample, as well as sorbents, their properties, and the diverse geometries of support materials employed in SPME. This review underscores the potential of emerging extraction protocols to further accelerate metabolomics research. • SPE is a standard technique for metabolite isolation in targeted metabolomics. • Choice of sorbent is crucial for SPE, depending on the properties of target analytes. • Emerging materials hold promise for enhanced selectivity in metabolite extraction. • Dispersive solid-phase extraction is a simple, versatile and efficient alternative. • Solid-phase microextraction enables in vivo sampling for metabolomic studies.