## 3 Results and Discussion
### Method Knowledge of Space  
#### 3.2.1 HS-SPME Fibers  
The HS-SPME/GC-MS methods previously described by our and other research groups provided the necessary knowledge for defining the CMPs range, before the investigation of the knowledge space (KS) [12; 23; 24]. Taking into account the obtained results, a fractional factorial design (FFD) based on a 4\({}^{3-1}\)-level model was applied as the design of the experiment (DoE) for HS-SPME-KS screening, being evaluated by the following parameters: NaOH concentration (5, 15, and 25 M), extraction temperature (25, 35, and 45 \({}^{\circ}\)C), extraction time (5, 25, and 45 min), and NaCl percentage (10%, 30%, and 50%). DoE was used for each of the studied fiber types (DVB/CAR/PDMS, CAR/PDMS, and PDMS/DVB). The results are presented in Table S4 (Supplementary Material). The TPA and IP results for each fiber under the optimal extraction conditions are shown in Figure 1(a) and (b), respectively. According to the results, all fibers were capable of extracting TMA and DMA, which is in agreement with the results obtained by [PERSON] (2006) [12]. However, they showed variable extraction efficiency. The efficiency of the fibers for TMA and DMA extraction followed the order DVB/CAR/PDMS \(>\) CAR/PDMS \(>\) PDMS/DVB. From the obtained data, CAR/PDMS and PDMS/DVB fibers showed better results when the extraction parameters were in their higher range conditions corresponding to runs 24 and 22, respectively. The DVB/CAR/PDMS fiber presented the best results under milder extraction conditions (run 13), mainly in the extraction time, which was half of the time necessary for the other fibers. At their highest TPA values, the percentage of difference concerning DVB/CAR/PDMS fiber is 20% for CAR/PDMS and 64% for PDMS/DVB. For IP (%RSD), the total means for each fiber performed below the maximum acceptable value of 15% RSD, as presented in Table S4 (Supplementary Material). Only two conditions registered values in the limits of the maximum acceptable value, 15.0% for the DMA value with DVB/CAR/PDMS (run 18), and 15.4% for the TMA value with PDMS/DVB (run 16). These results reflect the fiber properties and amine characteristics as summarized in Table 1.  
Figure 1: Results from the HS-SPME knowledge space of extraction conditions (**a**) Total peak area analysis for all fibers; (**b**) Intermediate precision for all assayed fibers. Four parameters must be taken into consideration for fiber selection:  
1. Molecular weight and analyte size related to analyte speed; the smaller the analytes, the faster it moves, and the retention might be harder. Highly cross-linked fibers could better retain fast-moving analytes. 2. Analyte polarity is defined by the type of coating and its ability to retain analytes according to polarity. However, each fiber has a certain capacity that might be better suited for ones than others. 3. Analyte concentration level and range-thicker fibers might require higher concentrations of an analyte to be more efficient. 4. The complexity of the sample-related to the analyte displacement by the other sample components with higher affinity or concentration. Considering the properties of the fiber, the thicker ones will require more time to reach the equilibrium and a high analyte concentration present in the headspace, and consequently harder extraction conditions (i.e., temperature, extraction time, alkaline conditions, and ionic strength (salt addition). Pore size also influences the compound molecular weight range and its capability to be retained. Thicker coatings tend to be more efficient; however, longer times are required to achieve equilibrium and to analyte desorption. On the other hand, the efficiency of the fiber increases with the decrease in film thickness [37; 38; 39]. PDMS/DVB showed the lowest extraction efficiency, expressed by the lowest amount of extracted TMA and DMA. Additionally, its lower cross-linked structure decreases the extraction efficiency of low molecular and highly volatile analytes, such as TMA and DMA [37; 39].