Innovative ion mobility - mass spectrometry workflows for discovering veterinary drug metabolites in tissues and the creation of sensitive methods for their quantification.

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Ensuring food is safe is a public health priority; detection of banned substances are of particular concern as they are often illegally used and can lead to serious adverse health effects in humans, such as cancer. Having accurate and sensitive methods is vital in food safety and consequently, liquid chromatography - mass spectrometry (LC-MS) has become an essential tool due to its high sensitivity and selectivity for analyzing biological samples. The workflow we are developing for analyzing veterinary drug residues involves two main steps; identification and quantification of a suitable drug residue. Within both these steps, biological matrices typically produce very complex mass spectra, which adversely affects selectivity and detection limits. Ion mobility devices help alleviate issues caused by the biological matrix since the separation mechanism of ion mobility differs from both LC and MS. Thus, combining ion mobility with LC-MS leads to a greater separation capacity that simplifies complex analyses. Our workflow employs high-field asymmetric waveform ion mobility spectrometry (FAIMS) in both steps since LC-FAIMS-MS offers very high sensitivity and selectivity. A collaborative effort between Thermo Fisher and my group led to the development of a new FAIMS interface (FAIMS Pro) that addressed initial challenges with FAIMS. However, FAIMS Pro was designed primarily for proteomics where complete ion desolvation readily occurs. For small molecule applications that use high liquid flow rates, a thorough investigation of critical parameters, most notably solvent effects and the integration of gas modifiers, is needed. Developing an optimized FAIMS device for small molecule analysis is a critical step in my proposed research. An investigation of solvent effects combined with the use of gas modifiers in FAIMS, will be used to develop an approach to allow solvated ions to enter FAIMS without adversely affecting sensitivity or robustness. This will be an integral part of a joint effort with Thermo Fisher to redesign the FAIMS Pro device for use specifically with small molecules (sFAIMS) thereby enabling maximal sensitivity by allowing significantly more ions into FAIMS. Integration of sFAIMS into our food safety workflows will improve upon both steps; primarily for overcoming chemical background issues for problematic analytes in quantitative methods, but also in the identification step in using the extra separation capacity to assist the software in extracting suitable drug residues for quantification from complex matrices. In addition to using the workflow for veterinary drug residues in food and tissue, the adaptability makes it amenable to other food safety applications such as food authenticity. Longer term, the workflow can be readily adapted for use in other fields in which high selectivity and sensitivity are required, for example, in identifying and quantifying disease biomarkers in health and medicine.