## 4 Extraction Methods  
Tables 2 and 3 provide an overview of the extraction methods that have been employed before the analysis of 4(5)MEI with LC and GC, respectively. In addition, the conditions of the chromatographic methods, as well as the LOQs and the method recoveries, are listed with the aim of assisting the researchers in evaluating each method and choosing the appropriate extraction and analysis conditions for the determination of 4(5)MEI. Several studies have reported a simple dilution of samples with water without a subsequent clean-up procedure prior to the LC analysis (Table 2). This practice has been applied in caramel color [19; 23; 78], beverages [33; 34; 36; 41], and vinegar [33]. Other extraction solvents that have been used are acetonitrile (ACN) [28; 39], methanol (MeOH)/water (50/50 \(v\)/\(v\)) [35], MeOH/formic acid [32], ammonium formate in water [31], and the mobile phase of the LC method [38]. The extract clean-up has been achieved by simple filtration [39; 40; 79]. Nevertheless, the primary extract clean-up procedure is solid phase extraction (SPE). Cartridges with strong cation exchange sorbents are used, which are functionalized with aromatic sulfonic acid (SCX and MCX) or propyl sulfonic acid (PCX). The SPE method is usually applied after the employment of liquid extraction of 4(5)MEI from food matrices [10; 17; 18; 22; 24; 25; 26; 29; 32; 37]. Extracts are acidified before loading onto the SPE cartridges. The cartridges are usually conditioned and equilibrated with MeOH and water with or without acid addition. After the loading of the extract, the cartridges are flushed with acidified water and MeOH. Elution of 4(5)MEI is performed using the ammonia solution in MeOH [22; 26; 29; 32; 33] or ACN/water [24]. [PERSON] et al. [30] used a dispersive micro SPE with PCX sorbent to replace the traditional SPE method, simplifying the clean-up procedure. The QuEChERS technique has also been employed for the extraction of 4(5)MEI from soft drinks, bakery products [25], and soy sauce [27]. This green extraction method was devised in 2003 and utilizes a solid sorbent that is added directly into the sample solution to absorb the interference components [80]. Molecularly imprinted polymers (MIPs) have been successfully applied for the extraction of 4(5)MEI. [PERSON] et al. [20] utilized as a template molecule, 4-methylimidazole, in order to prepare a new imprinted polymer for the design and synthesis of alkyl-imidazolium ionic liquid-imprinted polymers. Other research studies have used MIPs for the extraction of 4(5)MEI from beverages [23] and soy sauce [81]. Finally, two studies employed a derivatization reaction with dansyl chloride (Figure 2) prior to the LC analysis, in order to achieve lower detection and quantification limits for the determination of 4(5)MEI in biscuits [82] and beverages [22]. Figure 2: Derivatization reaction of 4(5)MEI with dansyl chloride. \begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline
**Matrix** & **Extraction** & **and Clean-Up** & **Detector** & **Column** & **Mobile Phase** & **Gradient** & **Flow Rate** & **LOQ** & **Recovery** & **Reference** \\ \hline \multirow{2}{*}{**Method**} & **Method** & **Precision** & **Precision** & **Precision** & **Precision** & **Precision** & **Precision** & **Precision** & **Precision** \\  & **and Clean-Up** & **Detector** & **Column** & **Mobile Phase** & **Gradient** & **Precision** & **Precision** & **Precision** & **Precision** \\ \hline  
\begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline  
\begin{table}
\begin{tabular}{c c c c c c c c c c} \hline \hline
\begin{tabular}{c} NEMD