Optimization of Mass Spectrometry parameters for Emerging Contaminants detection: A comparative study of Triple Quadrupole and Q-TOF analizers

Emerging contaminants (ECs) are a broad group of substances whose presence in the environment has attracted the attention of the scientific community over the last two decades [1]. Given the extremely low concentrations of ECs and the presence of interfering substances in environmental matrices, sophisticated instrumentation, such as liquid chromatographic coupled to mass spectrometry, is often required to achieve the necessary levels of specificity, accuracy, sensitivity and precision [2]. In this work, we propose the optimization of MS parameters for the consequent comparison of two HPLC-MS methods involving different tandem mass spectrometry (MS/MS) configurations: QqQ (Triple quadrupole) and Q-TOF (Quadrupole-Time of Flight). A total of 45 analytes were investigated, and due to their diverse properties, a multivariate experimental design was employed to assess multiple factors influencing sensitivity [3]. Chromatographic peak area was used as the response variable. For QqQ method optimization, a Face-Centered Composite Design (FCCD) was applied after a targeted study of MRM conditions for each analyte. Gas Temperature, Gas Flow, and Capillary Voltage were varied within the experimental domain. Model validation confirmed that all variables significantly influenced ionization efficiency, albeit to different extents. Q-TOF optimization required a broader set of variables, since the instrument is equipped with a Jet-Stream source, including Gas Temperature, Gas Flow, Sheath Gas Flow, Capillary Voltage, Fragmentor, and Mobile Phase Flow. Given the high number of factors, a Plackett-Burman screening was first conducted, followed by a FCCD. The most significant variables were Sheath Gas Flow, Capillary Voltage, and Fragmentor. The optimized methods were compared in terms of specificity, sensitivity and precision. The Q-TOF, operating in MS/MS mode, exhibited the highest specificity, which is crucial for complex matrices to minimize interferences. However, the QqQ, while maintaining high specificity, demonstrated significantly lower Limits Of Detection (LOD) and superior precision. The results of this comparison indicate that the QqQ is the optimal choice for the quantitative analysis of ECs in complex matrices. However, it is important to highlight the significant potential of the Q-TOF for suspect screening or untargeted analyses. Therefore, the optimized methods will be applied to the analysis of real samples for different purposes: the Q-TOF will be used for suspect screening, while the QqQ will enable targeted quantification of specific ECs. In conclusion, the experimental design approach proves to be fundamental to optimize the parameters in the two mass spectrometry configurations, allowing a more precise comparison of their performances. This ensures the selection of the most sensitive, specific and robust method for detecting emerging contaminants, offering more effective tools to address environmental challenges.