Optimization of Mass Spectrometry parameters for Emerging Contaminants detection: A comparison 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. This term can be referred to “contaminants that have only recently appeared”, but also to “contaminants of emerging concern” or rather substances that have been in the environment for some time, but concerns about them have only arisen recently [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]. Using an experimental design approach, we propose the optimization of mass spectrometry parameters in two LC-MS methods aimed at detecting emerging contaminants. These methods involve the use of high-performance liquid chromatography coupled with two different tandem mass spectrometry (MS/MS) configurations: QqQ (triple quadrupole) and Q-TOF (Quadrupole-Time of Flight). Both configurations are commonly used to analyse emerging contaminants in different matrices, but they serve different purposes. The QqQ configuration allows for target analysis with high specificity, whereas the Q-TOF configuration enables the analysis of molecules without knowing them a priori. However, the vast potential of the Q-TOF system comes with a potential trade-off, related to a reduced sensitivity. This study aims to compare the performance of the two individually optimized methods, focusing on this potential trade-off and examining instrumental precision. Additionally, it is important to note that these two systems ensure specificity through different mechanisms. The QqQ system achieves specificity by tracking distinct precursor-product transitions for each compound, whereas the Q-TOF system achieve this by measuring the exact mass [3]. Thus, in the first case, the entire ion pathway (including tandem MS parameters) within the spectrometer is optimized, whereas in the latter, the focus is primarily on the ionization of the molecules in the source. A total of 45 analytes were investigated, and given the variety in their properties, a multivariate experimental design approach was employed to simultaneously examine several factors that could affect the sensitivity [4]. In all cases, the chosen response was the chromatographic peak area. Regarding method optimization for the QqQ, a Face-Centered Composite experimental design was conducted, after a specific study of the MRM conditions for each analyte. The factors, varied within a selected experimental domain, were Gas Temperature, Gas Flow, and Capillary Voltage. The resulting models were validated and all variables were found to significantly affect ionization efficiency, albeit to varying extents. For the optimization of the Q-TOF method, due to its Jet-Stream type source, a larger number of variables had to be considered: Gas Temperature, Gas Flow, Sheath Gas Flow, Capillary Voltage, Fragmentor, and Mobile Phase Flow. Given the high number of factors, a Plackett-Burman screening design was initially used to evaluate which variables might be significant without considering their interactions. The most significant variables were Sheath gas Flow, Capillary voltage, Fragmentor and the Mobile phase Flow. After identifying the significant factors, a quadratic design will be employed to complete the study. In conclusion, the experimental design approach proves to be fundamental to optimize the mass parameters in the two mass spectrometry configurations, allowing a more precise comparison of their performances. This will ensure choosing the most sensitive and specific method for emerging contaminants determination, thus providing more powerful tools to address evolving environmental challenges.