## 3 Analytical Instrumentation
### Mass Spectrometry: Interfaces and Analysers  
Mass spectrometry (MS) is a widely used instrumental technique that is based on the ionization and fragmentation of sample molecules in the gas phase. MS has become the choice technique for the definitive identification of a wide variety of environment contaminants, including PhACs. In most cases, the separation of the compounds is achieved via chromatography (GC or LC) and the mass spectrometer is used as the detector. The separated compounds sequentially enter the mass spectrometer for the ionization, separation, and detection of the generated ions. The coupling of the chromatography system to the mass spectrometer allows for obtaining the retention time and mass spectral information for each separated compound, both of which can be compared with suitable reference standards [181]. The type of ionization in MS mainly depends on the internal energy transferred during the ionization process and on the physicochemical properties of the analyte to be ionized. Some ionization techniques are highly energetic and they produce extensive fragmentation. Other techniques are \"smooth\", with little fragmentation and only produce ions of the molecular species. Electronic ionization (EI), chemical ionization (CI), and field ionization (FI) are techniques that can only be applied to gas-phase ionization and, consequently, to compounds that are sufficiently volatile and thermally stable. However, because most PhACs are thermally labile and low volatile, the molecules of these compounds must be directly extracted from the condensed phase (liquid or solid) to the gas. These sources of direct ionization are of two types: ion sources in the liquid phase and in the solid phase. The first are those used in association with liquid chromatography, where the analytes are in solution. The solution is introduced by nebulization in the form of drops in the source, where ions are produced at an atmospheric pressure and subsequently focused on the mass spectrometer through differential pumping systems. Electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI) are sources of liquid phase ionization [181]. All of these ionization techniques have been applied to the analysis of PhACs. Relative to pharmaceuticals determination, the ESI is the most used technique, but there are some analytical methods with APCI. Electrospray ionization proves to be a more sensitive technique than APCI; however, it is more susceptible to matrix effects, thus becoming a less robust technique [182; 183]. There are few papers that report the use of APCI source for the ionization of moderate polar contaminants, such as PhACs, in water matrices. The target compoundsunder study belong to some therapeutical classes, such as anti-epileptic [184], antibiotics [185; 186; 187], NSAIDs [182], psychostimulants [188], benzodiazepines [183], and steroidal hormones [189; 190]. Other technological solutions have also been studied to improve high throughput of environmental analysis by making conventional ionization interfaces more efficient. For example, the laser diode thermal desorption-atmospheric pressure chemical ionization (LDTD-APCI) apparatus has eliminated the use of a LC/GC step prior to detection, thereby reducing sample pre-treatment, analysis time, and cost, eliminating chromatography columns, and reducing solvent consumption, while increasing sample throughput [191; 192]. In addition to these advantages, this technology also allows for the quantification in situ, which is essential in mapping contaminated areas and monitoring remediation effects. However, the direct analysis of heterogeneous and complex samples does not allow a precise and exact analysis of certain target compounds, mainly in trace concentration. Therefore, these techniques are most indicated to screen and control organic contaminants by semi-quantitative analysis [78].