A Novel UHPLC-MS Method Targeting Urinary Metabolomic Markers for Autism Spectrum Disorder
Autor: | Jaroslav Galba, Katarina Babinska, Juraj Piestansky, Daniela Ostatníková, Gabriela Repiská, Hana Celušáková, Stanislav Katina, Andrej Kovac, Dominika Olesova |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Arginine Endocrinology Diabetes and Metabolism lcsh:QR1-502 autism spectrum disorder Urine Pharmacology Biochemistry lcsh:Microbiology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics medicine liquid chromatography oxidative stress Xanthurenic acid Purine metabolism Molecular Biology mass spectrometry gut microbiota business.industry medicine.disease metabolomics 3. Good health Biomarker (cell) 030104 developmental biology chemistry Autism spectrum disorder Autism business 030217 neurology & neurosurgery |
Zdroj: | Metabolites Volume 10 Issue 11 Metabolites, Vol 10, Iss 443, p 443 (2020) |
ISSN: | 2218-1989 |
Popis: | Autism spectrum disorder is a heterogeneous neurodevelopmental disease. Currently, no biomarker of this disease is known. Diagnosis is performed through observation, standardized behavioral scales, and interviews with parents. In practice, diagnosis is often delayed to the average age of four years or even more which adversely affects a child&rsquo s perspective. A laboratory method allowing to detect the disorder at earlier stages is of a great need, as this could help the patients to start with treatment at a younger age, even prior to the clinical diagnosis. Recent evidence indicates that metabolomic markers should be considered as diagnostic markers, also serving for further differentiation and characterization of different subgroups of the autism spectrum. In this study, we developed an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the simultaneous determination of six metabolites in human urine. These metabolites, namely methylguanidine, N-acetyl arginine, inosine, indole-3-acetic acid, indoxyl sulfate and xanthurenic acid were selected as potential biomarkers according to prior metabolomic studies. The analysis was carried out by means of reversed-phase liquid chromatography with gradient elution. Separation of the metabolites was performed on a Phenomenex Luna® Omega Polar C18 (100 × 1.0 mm, 1.6 µ m) column at a flow rate of 0.15 mL/min with acetonitrile/water 0.1% formic acid aqueous as the mobile phase. The analysis was performed on a group of children with autism spectrum disorder and age-matched controls. In school children, we have detected disturbances in the levels of oxidative stress markers connected to arginine and purine metabolism, namely methylguanidine and N-acetylargine. Also, products of gut bacteria metabolism, namely indoxyl sulfate and indole-3-acetic acid, were found to be elevated in the patients&rsquo group. We can conclude that this newly developed method is fast, sensitive, reliable, and well suited for the quantification of proposed markers. |
Databáze: | OpenAIRE |
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