## 2 Results and Discussion
### Analytical Validation  
Analytes were detected by ESI-MS/MS in the SRM and in the positive ionization modes. The protonated molecules of the analytes [M + H]\({}^{+}\) were fragmented by collision-induced dissociation (CID). Two product ions of each analyte were selected as transitions in the SRM detection mode: one for quantitative and the other for qualitative purposes (Table 2). \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Analyte**} & **Precursor Ion (\(m\)/z)** & **Quantifier Ion (\(m\)/z)** & **Ce (eV)** & **DP (eV)** & **Qualifier Ion (\(m\)/z)** & **Retention Time** \\ \hline Chlorpromazine & 319.0 & 85.9 & 38 & 18 & 57.9 & 9.27 \\ Chlorpromazine-d3 & 324.0 & 60.9 & 34 & 42 & 89.0 & 9.25 \\ Clozapine & 327.0 & 270.0 & 44 & 30 & 191.9 & 8.62 \\ Olanzapine & 313.0 & 256.0 & 22 & 20 & 84.0 & 5.95 \\ Quetingine & 384.0 & 253.0 & 36 & 18 & 221.0 & 8.66 \\ Quetingine-d8 & 392.2 & 225.9 & 38 & 48 & 257.8 & 8.64 \\ Desmethyl chlorpromazine & 304.9 & 72.0 & 30 & 14 & 43.9 & 9.19 \\
7-hydroxy-chlorpromazine & 335.0 & 85.9 & 30 & 34 & 57.8 & 8.71 \\ \(N\)-desmethyl clozapine & 313.0 & 191.9 & 28 & 52 & 69.9 & 8.52 \\ \(N\)-desmethyl olanzapine & 299.0 & 197.9 & 26 & 28 & 212.9 & 5.46 \\ Norquetiapine & 296.0 & 209.9 & 54 & 26 & 138.9 & 8.61 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Ions transitions, instruments settings, and retention times for each antipsychotic and their metabolites. Figure 4: Fourier transform infrared spectrometry spectra of the poly(butyl methacrylate-co-ethylenediometabolic) monolith capillary. Method selectivity was assessed by comparing a blank plasma sample chromatogram with the chromatogram of a blank plasma sample spiked with the target analytes at concentrations corresponding to the lower limit of quantification (LLOQ) (Figure 5). The developed method was linear from the LLOQ (10 ng mL\({}^{-1}\)) to the upper limit of quantification (ULOQ) (200 ng mL\({}^{-1}\) to 700 ng mL\({}^{-1}\)); the coefficient of determination was higher than 0.9975 (Table 3). The lack-of-fit test confirmed method linearity. Calibration standards (\(n=5\)) presented coefficient of variation (CV%) lower than 15%. This linear range included therapeutic intervals. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Analyte**} & \multicolumn{3}{c}{**Linearity**} \\ \cline{2-4}  & \(\mathbf{R^{2}}\) & **Internal Standart** & **Lack of Fit Test** \\ \hline Chlorpromazine & 0.9986 & chlorporomazine-d3 & 0.848 \\ Clozapine & 0.9997 & quetiapine-d8 & 0.226 \\ Olanzapine & 0.9989 & quetiapine-d8 & 0.146 \\ Quietapine & 0.9981 & quetiapine-d8 & 0.888 \\ Desmethyl chlorpromazine & 0.9975 & chlorporomazine-d3 & 0.420 \\
7-hydroxy-chlorpromazine & 0.9992 & chlorporomazine-d3 & 0.166 \\ \(N\)-desmethyl clozapine & 0.9989 & quetiapine-d8 & 0.196 \\ \(N\)-desmethyl olanzapine & 0.9997 & quetiapine-d8 & 0.955 \\ Norquetiapine & 0.9985 & quetiapine-d8 & 0.115 \\ \hline \hline \end{tabular}  
* \(\mathbf{r}\)-value at a significance level of 0.05.  
\end{table} 
Table 3: Linearity of the SPME-UHPLC-MS/MS method. Figure 5: LC-MS/MS TIC (Total Ions Current) chromatograms of a drug-free plasma sample (subscript on the left) and drug-free plasma sample spiked with target drugs at the LLOQ concentrations. The developed method presented accuracy, with RSE values ranging from \(-19.4\) to \(19.9\%\) (intra-assay) and from \(-18.9\) to \(19.3\%\) (inter-assay), as well as precision, with CV values ranging from \(0.7\) to \(14.2\) (intra- and inter-assay) (Table 4). The method matrix effect was evaluated by using CV values of the IS-normalized matrix effect that were lower than \(15\%\) (Table 4). Residual carryover in blank plasma samples following ULQQ analysis exhibited values lower than \(3\%\) of the analyte LLOQ signal, or \(0.05\%\) of the IS LLOQ signal. Comparing the in-tube SPME-UHPLC method with literature methods (Table 5), the proposed method presented lower LLOQ values than the values obtained with the MEPS-UHPLC [26] method.