## 4 Methods Validation
Usually, the acceptance criteria for different analytes are similar if the analytical methods and samples' concentrations are similar. A brief evaluation of the validation parameters is done, focusing on the main problems or limitations that are found in the literature. Target compounds analyzed by the same or different methods show different linear profile when analyzed by other researchers. After the linearity study, the working range must be defined. According to ISO 8466-1 [232], the linear range should be evaluated in any quantification procedure, and several statistical parameters were defined, namely, determination coefficient (R\({}^{2}\)), coefficient of variation of the method (CVm), and Fisher Snedecor test (Mandel test). The R\({}^{2}\) is a good correlation indicator but is not a linear indicator. However, most researchers report linear studies based on R\({}^{2}\) and the other parameters are not quantified. Only a few reviews [10; 59] write the Mandel test. Usually, the PG and tabulated F values are missing. Another problem is the acceptable R\({}^{2}\). Some publications report values lower or equal to 0.98. To fit the requirement of PG lower than F (0.05; 1; N-3), the R\({}^{2}\) should be higher than 0.995, and the CVm should be lower than 5% [232]. In addition, some calibration curves have a broad range of concentration values, being higher than one magnitude order and not adjusted to the concentration of target compounds in samples. Some authors use the same calibration curve to quantify the target compounds in different matrix samples with very different concentrations. Therefore, the concentration range is not well adjusted to both samples. For example, PhACs in drinking water or wastewater [224; 225], or surface water and wastewater [45]. Nevertheless, the calibration curve's first concentration is not represented by the limit of quantification for each target compound. The matrix interference is a great problem in the quantification of PhACs in trace concentration in complex matrices. The quantification by external standard method is not adequate, due to matrix interferences. This is particularly relevant in quantitative analysis of environmental samples using chromatography coupled to mass spectrometry due to the suppression or the enhancement of the analyte signals in the presence of matrix components. The standard addition calibration or the matrix matched calibration is often used. Even in these conditions, instrumental analysis has problems of response linearity over wide concentration ranges, especially in the analysis of complex matrices, such as surface or wastewater, especially when the matrix components can act differently, depending on the level of analyte concentration [78; 235]. Standard addition calibration (SAC) is the most suitable method for compensating matrix effects, but it is time-consuming and laborious [10; 48]. Therefore, other methods have been proposed, such as internal standard calibration (ISC) and matrix-matched calibration (MMC). The most versatile approach is to use isotopically labeled standards (ISC) [166; 167; 236]. This approach has been considered the best option for compensating signal suppression or enhancement in mass spectrometry. It uses isotope-labeled analogues for quantitative analysis. In LC-MS/MS analysis, it is expected that the ionization of the target analytes and the isotope-labeled analogues will be suppressed or enhanced to the same extent, as the analogues should have the same chromatographic retention times and ionization characteristics as the analytes (184). However, these standards may be expensive, and they are often not commercially available for environmental analysis. Sometimes it is possible to use structurally similar unlabeled compounds as internal standards that do not coelute with the analytes of interest [235]. Concerning the limit of detection (LOD) and limit of quantification (LOQ), most of the publications report their values that are based on a signal-to-noise ratio (S/N) of 3 and 10, respectively [10; 96; 222].