Solid-Phase Extraction (SPE) is a sample pretreatment technology, developed from the combination of liquid-solid extraction and liquid chromatography column, and is mainly used for sample separation, purification and concentration. Compared with the traditional liquid extraction method, the recovery rate of the analyte can be improved, the analyte can be separated from the interfering components more effectively, the sample pretreatment process is reduced, and the operation is simple, time-saving and labor-saving. Liquid liquid extraction is mainly used for some weakly polar or non-polar targets. It is not applicable to those targets with too strong polarity or ionic targets, and there is no impurity removal process. The treated samples will contain non-polar impurities, which will not only pollute the chromatographic column and instrument, but also cause a certain matrix effect. In theory, solid-phase extraction can be applied to non-polar, polar, and ionic targets. This is also the reason why solid-phase extraction technology has become more and more popular in recent years.
SPE solid-phase extraction is divided into categories according to the retained substances: one is to retain the target compound; the other is to retain the impurities (similar to the pre-treatment operation of QuEChERS). SPE solid phase extraction is divided into three categories according to the type of packing: non-polar retention type; polar retention type; ion exchange type. The following figure shows the SPE processing process.

Step 1: Activation
SPE generally uses a certain volume of organic reagents and a certain volume of water-soluble reagents to step through the column to achieve the activation process. Activation serves two purposes:
- Through the organic reagent and water-soluble reagent through the column to remove some of the impurities in the column, to avoid system pollution and influence on the sample loading effect.
- The functional groups on the surface of the packing are more orderly spread out, and the contact area of the loading liquid is increased to play a better role in retention.
The structure arrangement of the polymer before activation is irregular, and many structures are tightly hugged together like “balls of wool”. This will cause a lot of functional groups to be wrapped in the “coil”, which can not make good contact with the target and play a retention role. Therefore, after activation, the arrangement of these structures will become very orderly, and the contact area with the target will be increased, and the target will be well retained.

Step 2: Sample Loading
After activation, we can load the pre-processed sample. After the sample is loaded, the target will be firmly retained on the SPE filler. Of course, some impurities with similar properties to the target will be retained on the SPE. The remaining impurities will flow out directly with the sample liquid.
Step 3: Rinsing
As the name suggests, the purpose of elution is to elute the impurities, avoid the pollution of chromatographic columns and instruments, and reduce the interference of impurities to the detection of target objects. This reduction of interference is the so-called reduction of matrix effect
Step 4: Elution
Elution is the use of reagents to destroy the force between the target and the packing, so as to separate and collect the target from the packing.
Step 5: Reconstituted by nitrogen blowing
This process is an optional step, and there are usually two situations that require nitrogen blowing and reconstitution operation. One is that the eluent is quite different from the initial mobile phase. If the sample is injected directly, there may be a serious solvent effect that affects the peak shape. Therefore, it needs to be dried with nitrogen and reconstituted with the initial mobile phase and then injected for analysis. Second, when the detection sensitivity of the instrument does not meet the actual sample analysis requirements, it can be reconstituted with a small volume of reconstituted solution after the nitrogen is blown dry, and the target substance concentration is increased before sample analysis.
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