Bringing CE-MS into the regulatory toxicology toolbox: Application to neuroinflammation screening

Article Article scientifique Article Bringing CE-MS into the regulatory toxicology toolbox: Application to neuroinflammation screening eng 2023-10 author Tobolkina Elena 916747 author Pamies David 952168 author Zurich Marie-Gabrielle 0000-0002-3168-5968 author Rudaz Serge 0000-0002-4180-5417 28978 Section des sciences pharmaceutiques (FARMA) author Gonzalez Ruiz Victor 0000-0001-7204-2363 831974 109048 10.1016/j.microc.2023.109048 0026-265X https://linkinghub.elsevier.com/retrieve/pii/S0026265X23006677 Despite its suitability to analyze polar metabolites using minute amounts of sample and its large peak capacity, CE-MS has traditionally been considered to lack the robustness required by untargeted metabolomics, especially in regulatory environments. This belief comes from the difficulty to adequately identify metabolites based on their migration times due to the variability of such parameter. In the present work, we demonstrate how this limitation can be circumvented by using standardized CE-MS conditions and automatically converting CE-MS files into electrophoretic mobility (μeff) scale. This strategy allows to conveniently exploit the advantages of CE-MS for low-volume samples generated during the toxicological risk assessment of potential neuro- inflammatory substances, performed via the evaluation of astrocyte reaction. Human astrocyte cells were exposed to tumor necrosis factor alpha (TNFα) as a model compound and to digoxin at different concentrations as a tested chemical. The induced metabolic profiles were then characterized by means of CE-MS metabolomics and the success of the annotation step was evaluated and compared when one or two reference compounds were used as markers for the conversion into the effective electrophoretic mobility scale. The use of two markers resulted in a more reliable metabolite identification across all the conditions. As a result, a total of 68 anionic and cationic metabolites were annotated in both CE polarities. Unsupervised and supervised multivariate analysis enabled the comparison of the metabolomic profiles induced by each compound, highlighting common and differential metabolites, suggesting a similar but specific mechanism of activation for digoxin with regard to TNFα. CE-MS- based metabolomics is an advantageous tool for the analysis of minute amounts of samples delivered by new approach methodologies (NAMs) in chemical risk assessment, allowing high throughput toxicity screening. Capillary electrophoresis Effective mobility Astrocytes Annotation Untargeted metabolomics Low volume-sample analysis Dewey 615 31 Section des sciences pharmaceutiques 17 false 881 Sciences analytiques Microchemical journal 193 4fe60052-6cb4-414f-ae52-603c9b418bd4 Article (Published version) Restricted 1-s2.0-S0026265X23006677-main.pdf 701859 application/pdf 7ff04b41ec45d33b19f318be29bb56a9d9262427fef0f8b47c22f8440b47cba2 restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Bringing CE-MS into the regulatory toxicology toolbox: Application to neuroinflammation screening	Microchemical journal			2023	77	0

Archive ouverte UNIGE

Pamies, David