RT Journal Article T1 Characterization of the Human Exposome by a Comprehensive and Quantitative Large-Scale Multianalyte Metabolomics Platform. A1 Gonzalez-Dominguez, Raul A1 Jauregui, Olga A1 Queipo-Ortuño, Maria Isabel A1 Andres-Lacueva, Cristina K1 Mass Spectrometry K1 Metabolome K1 Metabolomics K1 Olive Oil AB The exposome, defined as the cumulative measure of external exposures and associated biological responses throughout the lifespan, has emerged in recent years as a cornerstone in biomedical sciences. Metabolomics stands out here as one of the most powerful tools for investigating the interplay between the genetic background, exogenous, and endogenous factors within human health. However, to address the complexity of the exposome, novel methods are needed to characterize the human metabolome. In this work, we have optimized and validated a multianalyte metabolomics platform for large-scale quantitative exposome research in plasma and urine samples, based on the use of simple extraction methods and high-throughput metabolomic fingerprinting. The methodology enables, for the first time, the simultaneous characterization of the endogenous metabolome, food-related metabolites, pharmaceuticals, household chemicals, environmental pollutants, and microbiota derivatives, comprising more than 1000 metabolites in total. This comprehensive and quantitative investigation of the exposome is achieved in short run times, through simple extraction methods requiring small-sample volumes, and using integrated quality control procedures for ensuring data quality. This metabolomics approach was satisfactorily validated in terms of linearity, recovery, matrix effects, specificity, limits of quantification, intraday and interday precision, and carryover. Furthermore, the clinical potential of the methodology was demonstrated in a dietary intervention trial as a case study. In summary, this study describes the optimization, validation, and application of a multimetabolite platform for comprehensive and quantitative metabolomics-based exposome research with great utility in large-scale epidemiological studies. PB American Chemical Society YR 2020 FD 2020-09-23 LK https://hdl.handle.net/10668/26679 UL https://hdl.handle.net/10668/26679 LA en NO González-Domínguez R, Jáuregui O, Queipo-Ortuño MI, Andrés-Lacueva C. Characterization of the Human Exposome by a Comprehensive and Quantitative Large-Scale Multianalyte Metabolomics Platform. Anal Chem. 2020 Oct 20;92(20):13767-13775 NO This work has received funding from the Spanish Ministry ofEconomy and Competitiveness (MINECO) (Nos. PCIN-2015-229, PCIN-2015-238, and PCIN-2017-076) under theumbrella of the European Joint Programming Initiative “AHealthy Diet for a Healthy Life” (JPI HDHL, http://www.healthydietforhealthylife.eu), CIBERFES and ISCIII projectsAC19/00111 and AC19/00096 (cofunded by the FEDERProgram from EU, “A Way To Make Europe”), and from theGeneralitat de Catalunya’s Agency AGAUR (2017SGR1546).R.G.-D. thanks the “Juan de la Cierva” program from MINECO (No. FJCI-2015-26590) and C.A.-L. acknowledgesthe ICREA Academia Award 2018. M.I.Q.-O. is the recipientof a “Miguel Servet Type II” fellowship (No. CPI13/00003from ISCIII, cofunded by FEDER) and also belongs to theregional “Nicolas Monardes” research program (No. C-0030-2018, Junta de Andalucí a, Spain). Authors thank to Prof. PaulKroon (Quadram Institute Bioscience), Prof. Daniele Del Rio(University of Parma), and Prof. Kati Hanhineva (Universityof Eastern Finland) for kindly providing synthesized in-housestandards DS RISalud RD Apr 5, 2025