## 5 Instrumental Analysis
### Detection Methods  
The detection of NIAS in plastic FCMs relies on MS platforms tailored to the physico-chemical properties of migrants, with HRMS and hybrid systems serving as the cornerstone for sensitivity, selectivity, and structural elucidation. The reviewed studies emphasize the critical role of mass analyzer selection, ionization modes, and acquisition strategies in addressing the complexity of NIAS, ranging from low-molecular-weight volatiles to high-molecular-weight oligomers. HRMS systems, including QTOF and Orbitrap analyzers, dominate non-targeted screening due to their ability to deliver accurate mass measurements (<5 ppm exact mass error) and isotopic profiles for elemental formula assignments. For example, [PERSON] et al. [6] employed UHPLC-QTOF-MS in MS\({}^{\mathrm{E}}\) mode, an advanced DIA approach, which enables the simultaneous acquisition of MS/MS fragmentation spectra at low and high collision energies (CEs) during the same run. Similarly, [PERSON] et al. [23] utilized UHPLC-HRMS (Q-Orbitrap) to acquire one-dimensional full-scan (FS) data (120,000 FWHM) as well as targeted-MS\({}^{2}\) (15,000 FWHM) for structural elucidation. Orbitrap systems are particularly suitable for high-resolution applications, standing out for resolving isobaric compounds, as demonstrated by [PERSON] et al. [25], who operated HRMS using a combination of FS and data-dependent tandem mass spectrometry (ddMS\({}^{2}\)) modes. The FS mode employed a resolution of 120,000 FWHM with a scan range of 100-1000 \(m/z\). Between every two FSs, 10 ddMS\({}^{2}\) scans were acquired. The ddMS\({}^{2}\) analysis trigger algorithm was based on minimum ion intensity (1 \(\times\) 104) and a dynamic exclusion list. The ddMS\({}^{2}\) scan employed a resolution of 15,000 FWHM with an isolation window of 1 \(m/z\) and a stepped CE mode in higher-energy collisional dissociation. While QTOF systems offer slightly lower resolvingpower, they are often preferred for faster acquisition speeds and higher throughput, which can be advantageous for large-scale screening workflows. The high resolving power of these systems is particularly advantageous for polymer-derived NIAS, such as linear and cyclic oligomers. In this sense, non-targeted MS/MS acquisition allows for structural elucidation through precursor ion isolation and fragmentation, with both DIA and DDA modes (Figure 3). This improves identification confidence, particularly for isobaric or co-eluting compounds with unknown or overlapping fragmentation patterns. In the work conducted by [PERSON] et al. [20], UHPLC-QTOF-MS was used, applying DIA-MS2 in sequential windowed acquisition of all theoretical MS (SWATH) mode. By applying SWATH acquisition, the full \(m/z\) range of precursor ions is continuously stepped along average mass windows of 20-85 Da, obtaining MS/MS data of much narrower precursor ion ranges and facilitating the recording of all detectable peaks in a sample with high-quality deconvoluted fragment mass spectra. Compared to DDA, which relies on intensity-based precursor selection and may miss low-abundance signals, DIA (including SWATH) ensures comprehensive MS/MS coverage but imposes higher data processing demands. This includes an increased risk of false positives or misannotations due to the complex spectral deconvolution required when many co-eluting compounds are fragmented simultaneously. Figure 3: Schematic comparison between: (**A**) data-dependent acquisition (DDA) and (**B**) data-independent acquisition (DIA). As such, the choice between DIA and DDA depends on the sample complexity, target analyte profile, and available data analysis tools. Ionization methods are pivotal in determining the scope of NIAS detection, with ESI, EI, and atmospheric pressure chemical ionization (APCI) serving distinct roles based on analyte polarity and volatility. These ionization techniques collectively address the chemical diversity of NIAS.