## 3 Analytical Instrumentation
### High-Resolution Mass Spectrometry (HRMS)
[206] show the UPLC-Q Exactive TM Orbitrap MS's capability for simultaneous determination of 28 acidic and basic PhACs in a single run using rapid polarity switching of the electrospray ionisation source. The PhACs belong to seven therapeutical classes, such as antibiotics, beta-blockers, NSAIDsIDs, narcotic analgesics, anti-hyperglycemic, and proton-pump inhibitors. The method applies rapid polarity switching in the heated ESI source for the simultaneous analysis of positive and negative ionised compounds in one chromatographic run of 16 min. [PERSON] et al. [207] optimized the conditions of ultra-high pressure liquid chromatography hyphenated with a quadrupole Orbitrap mass spectrometer (UHPLC- Q-Orbitrap-MS) to analyze 13 PhACs in water matrices. High-resolution MS and MS/MS analysis produce high selectivity and sensitivity based on the exact mass measurement of protonated and fragment ions using a narrow mass extraction window. The optimization approaches were performed to develop an acceptable method that allows for high resolution analysis of a range of PhACs in water samples with reliable quantification and confirmation of compound identities. [PERSON] et al. [208] compared the most popular HRMS instruments, quadrupole time-of-flight and linear trap quadrupole-Orbitrap, from two different laboratories. Wastewater (influent and effluent) and surface water samples from Spain and Italy were screened for 107 PhACs and abuse drugs (including 220 fragment ions). The sample results and findings of both instruments were compared, highlighting the advantages and drawbacks of the strategies that were applied in each case. [PERSON] et al. [209] applied LC-Q Exactive Orbitrap high resolution MS in both full scan (FS) MS and targeted MS/MS modes to study the occurrence of 67 pharmaceutical and antifungal residues in the Danube river. [PERSON] et al. [210] screened 20 PhACs belonging to antibiotics, antipsychotics, anti-inflammatory drugs, plus acesulfame K with UHPLC-LTQ-Orbitrap MS in hospital and urban WWTP effluents. The method proved to be a powerful technique for the quantification and identification of analytes of interest in effluent matrix with excellent mass accuracies below 2 ppm and 5 ppm for positive and negative ionization, respectively. However, low-resolution (LR) mass spectrometers continue to be the most used due to this equipment's lowest price. Nevertheless, their properties make them suitable for high throughput targeted and screening approaches involving a significant number of PhACs [10; 23; 166; 211]. Triple quadrupole has still preserved its market share due to the competitive price and unequalled performances in quantitative analysis [212; 213; 214]. \begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline  
\begin{table}
\begin{tabular}{c c c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Matrix**} & \multirow{2}{*}{**N-PACs** **Trespeutical**} & \multicolumn{2}{c}{**Extraction**} & \multirow{2}{*}{**Phase System**} & \multicolumn{2}{c}{**Analytical In-transmutation**} & \multicolumn{2}{c}{**Stationary PhaseColumn**} & \multicolumn{1}{c}{**Cal/R\({}^{3}\)**} & \multicolumn{1}{c}{**Precision**} & \multicolumn{1}{c}{**Recovery**} & \multicolumn{1}{c}{**LOD/LOQ**} & \multirow{2}  
\begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline \multirow{2}{*}{**Matrix**} & \multirow{2}{*}{ \begin{tabular}{c} **N\({}^{*}\)PACs Theoretical** \\ **Classes** \\ \end{tabular}  } & \begin{tabular}{c} **Extraction** \\ **Configuration-Sample** \\ **Volume** \\ \end{tabular}  & **Phase System** & **Analytical Instrumentation** & **Stationary** & **Calc./R\({}^{2}\)** & **Precision** & **Recovery** & \begin{tabular}{c} LOD/LQQ \\ **(ng/L)** \\ \end{tabular}  & **Ref. ** \\ \hline \multirow{4}{*}{ \begin{tabular}{c} Surface water and wastewater \\ \end{tabular}  } & 7 PhACs & \begin{tabular}{c} SFE \\ (antidepressants) \\ \end{tabular}  & \begin{tabular}{c} **(MSED)** \\ 100 mL \\ \end{tabular}  & MIP & \begin{tabular}{c} UPLC-(OS)- \\ MS/MS \\ \end{tabular}  &