Pharmacokinetic profile of metabolites by heart-cutting two-dimensional liquid chromatography: A focus on paracetamol analysis

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography A Pub Date : 2025-02-09 DOI:10.1016/j.chroma.2025.465760

Ana Ballester-Caudet, Simón Mariño Perea, Diego García-Gómez, José Luis Pérez Pavón, Encarnación Rodríguez-Gonzalo

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引用次数: 0

Abstract

Therapeutic drug monitoring of paracetamol (acetaminophen, N-acetyl-p-aminophenol, APAP) metabolites in plasma and serum samples was conducted using two-dimensional liquid chromatography (2D-LC) by means of online heart-cutting passive modulation. The selective and efficient 2D-LC approach here developed was applied for the simultaneous determination of six paracetamol metabolites: its major metabolite, the glucuronide conjugate (APAP-GLUC), and its main transformation product p-aminophenol (PAP), along with the bioactive N-arachidonoylphenolamine (AM404), the reactive hepatotoxic N-Acetyl-p-benzoquinone imine (NAPQI), in addition to glutathione (APAP-GLUT) and protein-derived cysteine (APAP-CYS) conjugates. Online heart-cutting mode allowed the combination of C18 reversed-phase column in the first dimension and a Primesep SB analytical column (C18-anion exchange) in the second dimension promoting the effective separation of such different paracetamol metabolites, ranging from highly polar to extremely hydrophobic. The results suggest the promising potential of the proposed 2D-LC methodology for therapeutic drug analysis and pharmacokinetic studies.

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来源期刊

Journal of Chromatography A 化学-分析化学

CiteScore

7.90

自引率

14.60%

发文量

742

审稿时长

45 days

期刊介绍： The Journal of Chromatography A provides a forum for the publication of original research and critical reviews on all aspects of fundamental and applied separation science. The scope of the journal includes chromatography and related techniques, electromigration techniques (e.g. electrophoresis, electrochromatography), hyphenated and other multi-dimensional techniques, sample preparation, and detection methods such as mass spectrometry. Contributions consist mainly of research papers dealing with the theory of separation methods, instrumental developments and analytical and preparative applications of general interest.