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Optimization of gradient reversed phase high performance liquid chromatography analysis of acetaminophen oxidation metabolites using linear and non-linear retention model

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019132" target="_blank" >RIV/62690094:18470/22:50019132 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216275:25310/22:39918673

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S0021967322001546?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0021967322001546?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.chroma.2022.462956" target="_blank" >10.1016/j.chroma.2022.462956</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Optimization of gradient reversed phase high performance liquid chromatography analysis of acetaminophen oxidation metabolites using linear and non-linear retention model

  • Original language description

    Acetaminophen (paracetamol, APAP) is one of the most widely used drugs worldwide. Unfortunately, its overdose, which is caused by predominant oxidation of APAP, can lead to acute liver injury. In liver, oxidized APAP is conjugated with glutathione, leading to APAP-glutathione conjugate, which is metabolized to APAP-cysteine and APAP-N-acetylcysteine conjugates. Thus, all of those compounds could be used to monitor APAP metabolism in the overdosed patients. To date, only a limited number of rapid and accurate methods have been reported for the assessment of APAP oxidation metabolites using simple instrumentation, and thus this work was aimed at developing a fast and convenient gradient HPLC-UV/MS method. For this purpose, APAP conjugates with glutathione, cysteine, and N-acetylcysteine were synthesized, purified by preparative liquid chromatography, and characterized by NMR and high-resolution mass spectrometry. The gradient elution conditions were optimized using the window diagram approach and the effects of mobile phase composition and additives on separation and detection sensitivity were evaluated using two, i.e., linear and non-linear isocratic retention models. Quantitative parameters of the developed method were evaluated and the effectiveness, sensitivity, and specificity of the method were demonstrated on the analysis of human kidney HK-2 cell lysates, confirming the suitability of the method for routine use in studies on APAP toxicity.(c) 2022 Elsevier B.V. All rights reserved.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10406 - Analytical chemistry

Result continuities

  • Project

    <a href="/en/project/GA19-11867S" target="_blank" >GA19-11867S: Research on toxicity mechanism of S-conjugates of aminophenolic drugs</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Chromatography A

  • ISSN

    0021-9673

  • e-ISSN

    1873-3778

  • Volume of the periodical

    1669

  • Issue of the periodical within the volume

    April

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    11

  • Pages from-to

    "Article Number: 462956"

  • UT code for WoS article

    000782581100002

  • EID of the result in the Scopus database

    2-s2.0-85126562957