## 3 Results and Discussion
### Analytical Performance of the Method  
The analytical performance of the optimized QuEChERS methodology was evaluated in terms of linearity, precision, accuracy expressed as recovery, limits of detection and quantification (Table 1) in accordance with the Documents N\({}^{\circ}\) SANTE/11813/2017 and N\({}^{\circ}\) SANTE/12682/2019 [32,33] while the matrix effect was also investigated. Matrix effect was evaluated as it is well known that co-extracted and co-eluting matrix substances can seriously affect the analyte signals, by enhancing or suppressing the analyte responses. For this purpose, the slopes of (a) the calibration curve of the analytes spiked in milk extracts (matrix-matched standards) and (b) the analytes standard solutions were compared. The ratio (a/b \(\times\) 100) is defined as the matrix effect (ME %). A value of 100% means that there is no matrix effect. There is an enhancement if the value is >100% and signal suppression if the value is <100%. Matrix effect results (Figure S9) demonstrated that bisphenol A exhibited relatively low ionization suppression while both nonylphenol isomers and octylphenol showed a quite strong ionization enhancement. Therefore, matrix-matched calibration curves were used in the quantification to compensate for the matrix effect observed. The method linearity was evaluated by constructing method calibration curves (n = 2), after milk extraction under the optimum conditions, in the range of 0.1-200 ng g\({}^{-1}\). Good \begin{table}
\begin{tabular}{c c c c c c c} \hline
**EDCs** & **Linearity** & **R2** & **Rec \(\pm\)** & **Rec \(\pm\)** & **LOQ** & **LOD** \\  & **Range (ng** & & **RSD (\%)** & **RSD (\%)** & **ng g\({}^{-1}\)** & **ng g\({}^{-1}\)** \\  & **g\({}^{-1}\))** & & **5 ng g\({}^{-1}\)** & **50 ng g\({}^{-1}\)** & & \\ \hline BPA & 0.1–200 & 0.9987 & 101 \(\pm\) 4.2 & 97 \(\pm\) 0.9 & 0.1 & 0.05 \\ OP & 0.1–10/10–200 & 0.9998 & 101 \(\pm\) 11.7 & 91 \(\pm\) 6.3 & 0.1 & 0.05 \\ NP & 5–200 & 0.9966 & 99 \(\pm\) 6.7 & 96 \(\pm\) 2 & 5 & 1.5 \\
4 NP & 20–200 & 0.9999 & 108 \(\pm\) 6.4 & 100 \(\pm\) 3 & 20 & 5 \\ \hline \end{tabular}
\end{table} 
Table 1: QuEChERS-based analytical method performance in milk samples fortified with the target EDCs at two concentration levels. Figure 3: Response surface plots for the 2\({}^{3}\) central composite design (CCD). linearity was observed in the studied concentration range with correlation coefficients varying from 0.9966 to 0.9999. The precision determines the analytical deviation and is one of the most important criteria for evaluating analytical method performance. The intra-assay precision (repeatability) was determined within the same day and consisted of two series, and six replicates at the concentration level of 100 ng g\({}^{-1}\). Inter-assay precision (reproducibility) was calculated in two series, and six replicates at the same concentration within three different days. The repeatability and reproducibility of the target chemicals, both expressed as relative standard deviation, ranged from 0.6 to 13.3% and from 4.7 to 23.2%, respectively. Detection and quantification limits of the whole method were calculated as signal-to-noise ratios of 3 and 10, respectively. LOQs and LODs achieved were low enough in the range of 0.1-20 ng g\({}^{-1}\) and 0.05-5 ng g\({}^{-1}\) as expected when the analysis is carried out by HR instruments. To estimate the extraction method accuracy in terms of recoveries, milk samples previously fortified with the target analytes at two concentration levels, 5 and 50 ng g\({}^{-1}\), were extracted and analyzed in triplicates. Recovery values obtained for each analyte were high over the range of 91% (OP) to 108% (4 NP). Additionally, yogurt samples spiked at two concentration levels (10 and 50 ng g\({}^{-1}\)), were also extracted with the optimized method in order to investigate its applicability to other dairy products (Table S8).