Multitargeted Internal Calibration for the Quantification of Chronic Kidney Disease-Related Endogenous Metabolites Using Liquid Chromatography

Article Article scientifique Article Multitargeted Internal Calibration for the Quantification of Chronic Kidney Disease-Related Endogenous Metabolites Using Liquid Chromatography–Mass Spectrometry eng 2023-09-01 2023-09-01 author Visconti Gioele 0000-0003-2486-7744 School of Pharmaceutical Sciences, University of Geneva, CMU − Rue Michel-Servet 1, 1211 Geneva 4, Switzerland 783805 author De Figueiredo Miguel 0000-0003-4777-9130 School of Pharmaceutical Sciences, University of Geneva, CMU − Rue Michel-Servet 1, 1211 Geneva 4, Switzerland 727074 author Strassel Oriane 0009-0009-3387-7056 School of Pharmaceutical Sciences, University of Geneva, CMU − Rue Michel-Servet 1, 1211 Geneva 4, Switzerland 856435 Section des sciences pharmaceutiques (FARMA) author Boccard Julien 0000-0001-5913-9566 School of Pharmaceutical Sciences, University of Geneva, CMU − Rue Michel-Servet 1, 1211 Geneva 4, Switzerland 507373 Section des sciences pharmaceutiques (FARMA) author Vuilleumier Nicolas Department of Genetic and Laboratory Medicine, Geneva University Hospitals (HUG), Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland 61406 Département de médecine (DEMED) author Jaques David 0000-0003-3841-3049 Service of Nephrology, Geneva University Hospitals (HUG), Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland 633322 Département de médecine (DEMED) author Ponte Belen Service of Nephrology, Geneva University Hospitals (HUG), Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland 89158 Département de médecine (DEMED) author Rudaz Serge 0000-0002-4180-5417 School of Pharmaceutical Sciences, University of Geneva, CMU − Rue Michel-Servet 1, 1211 Geneva 4, Switzerland 28978 Section des sciences pharmaceutiques (FARMA) 13546-13554 10.1021/acs.analchem.3c02069 37655548 0003-2700 PMC10500547 https://pubs.acs.org/doi/10.1021/acs.analchem.3c02069 Accurate quantitative analysis in liquid chromatography–mass spectrometry (LC–MS) benefits from calibration curves generated in the same matrix as the study sample. In the case of endogenous compound quantification, as no blank matrix exists, the multitargeted internal calibration (MTIC) is an attractive and straightforward approach to avoid the need for extensive matrix similarity evaluation. Its principle is to take advantage of stable isotope labeled (SIL) standards as internal calibrants to simultaneously quantify authentic analytes using a within sample calibration. An MTIC workflow was developed for the simultaneous quantification of metabolites related to chronic kidney disease (CKD) using a volumetric microsampling device to collect 20 μL of serum or plasma, followed by a single-step extraction with acetonitrile/water and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Since a single concentration of internal calibrant is necessary to calculate the study sample concentration, the instrument response function was investigated to determine the best SIL concentration. After validation, the trueness of 16 endogenous analytes in authentic human serum ranged from 72.2 to 116.0%, the repeatability from 1.9 to 11.3%, and the intermediate precision ranged overall from 2.1 to 15.4%. The proposed approach was applied to plasma samples collected from healthy control participants and two patient groups diagnosed with CKD. Results confirmed substantial concentration differences between groups for several analytes, including indoxyl sulfate and cortisone, as well as metabolite enrichment in the kynurenine and indole pathways. Multitargeted methodologies represent a major step toward rapid and straightforward LC–MS/MS absolute quantification of endogenous biomarkers, which could change the paradigm of MS use in clinical laboratories. Calibration Chromatography, Liquid Humans Renal Insufficiency, Chronic / diagnosis Tandem Mass Spectrometry Dewey 615 Dewey 616 31 Section des sciences pharmaceutiques 17 56 Département de médecine 221 false 881 Sciences analytiques 211 Auto-immunité, inflammation et athérosclérose 270 Analytical chemistry 95 36 accb031b-8460-4594-a757-38c573041c3a Article (Published version) Public acs.analchem.3c02069.pdf 3208325 application/pdf CC BY-4.0 b6ca85436111864a258cf3b94bb2b06602eb3066dbbbd15d1ce3070847d585d3 6225cd64-27f3-4126-be0b-31cb6501f3d5 Supplemental data Public ac3c02069_si_001.pdf 1097156 application/pdf c2e432825ff4d2b211c3a1ef7a4566d06b6cd5fb2ef2624c8cba9ce0ba7129e4 Vignette Public images_large_ac3c02069_0006.jpeg 107625 openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de médecine

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Multitargeted Internal Calibration for the Quantification of Chronic Kidney Disease-Related Endogenous Metabolites Using Liquid Chromatography–Mass Spectrometry	Analytical chemistry			2023	133	60

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Strassel, Oriane