## 1 Introduction
The most common analytical instruments used to perform metabolomics are nuclear magnetic resonance (NMR) and mass spectrometry (MS), paired with either gas chromatography (GC-MS) or liquid chromatography (LC-MS) for separation prior to MS detection. Over time, however, MS-based platforms have become the preferred analytical technique in metabolomics due to their high sensitivity, comprehensive metabolite coverage, smaller sample volume requirements, and lower initial expense in comparison to NMR [6; 11]. LC separates analytes in a sample based on their interactions with the mobile and stationary phases, while MS measures the molecular weight of an analyte in relation to its charge (mass-to-charge [\(m/z\)] ratio). The capability of LC-MS to detect most semi- and non-volatile organic molecules from a range of biological fluids and tissues has rendered it the most utilized technique for capturing lipid metabolites [6; 12]. For example, [PERSON] et al. utilized LC-MS to identify a panel of serum phosphatidylcholine and phosphatidylcholine contamines capable of differentiating patients with early stage non-small cell lung cancer from healthy controls [13]. Similarly, [PERSON] et al. employed a targeted LC-MS/MS metabolomics approach to identify several plasma fatty acid metabolites as candidate markers of [PERSON]'s disease [14]. While negligible sample preparation is required for NMR-based metabolomics, sample preparation is especially important for GC-MS and LC-MS metabolomic platforms, as these techniques necessitate substantial sample clean-up to prevent clogging, fouling, or potential damage to the instruments [15; 16]. The aim of sample preparation in metabolomics is to establish an appropriate quenching mechanism and isolate metabolites of interest effectively and exclusively from complex samples [15; 16]. Traditional sample preparation techniques have included liquid-liquid extraction (LLE) and solid-phase extraction (SPE). Compounds are separated in LLE based on their solubilities in two immiscible liquids, while SPE employs a cartridge with a solid adsorbent to extract analytes from a sample [15; 17]. LLE is simple, fast, and does not require specialized equipment; however, the method requires a large solvent-to-sample ratio, uses environmentally toxic organic solvents, and is not easily automated [6]. SPE, on the other hand, consumes fewer environmentally toxic solvents, offers superior sample clean-up, and facilitates easier automation; however, the selection of a solid sorbent increases selectivity for specific metabolites, ultimately reducing the coverage of metabolite classes [6]. Unlike conventional sample preparation methods, solid-phase microextraction (SPME) is a novel, non-exhaustive technique that extracts only a small portion of free analytes from a sample [18]. A solid support (fiber) with a polymer coating is exposed to a sample for a preset amount of time, during which analytes migrate from the sample matrix onto the coating [19]. An equilibrium is then established between the fiber coating and sample matrix, whereby the amount of the analyte in/on the coating is proportional to the concentration of that analyte in the sample matrix [19]. Multiple forms of functionalized polymer particles with varying extraction capabilities exist for SPME [20]. After an extensive evaluation of multiple SPME coatings, [PERSON] et al. discovered that a combination of PS-DVB and HLB coatings extracted the largest range of analytes, including acidic, basic, and neutral compounds with a wide spectrum of log P values [20]. As such, SPME is a promising sample preparation method to perform prior to LC-MS untargeted metabolomic studies given its capabilities for non-selective extraction of a wide range of hydrophilic and hydrophobic metabolites from multiple forms of complex matrices (liquid, gaseous, and solid samples) [15; 19].