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

IF 4 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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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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切心二维液相色谱法代谢物药动学分析：对乙酰氨基酚分析的重点

采用二维液相色谱（2D-LC）在线切割心脏被动调制方法监测血浆和血清样品中扑热息痛（对乙酰氨基酚、n -乙酰基-对氨基酚、APAP）代谢物的治疗药物监测。本研究开发的选择性高效2D-LC方法用于同时测定六种对乙酰氨基酚代谢物：其主要代谢物葡糖苷偶联物（APAP-GLUC）及其主要转化产物对氨基酚（PAP）、生物活性n-花生四烯醇酚胺（AM404）、反应性肝毒性n-乙酰-对苯醌亚胺（NAPQI）、谷胱甘肽（APAP-GLUT）和蛋白质衍生半胱氨酸（APAP-CYS）偶联物。在线切心模式允许第一维的C18反相柱与第二维的Primesep SB分析柱（C18阴离子交换）相结合，促进了从高极性到极疏水的不同对乙酰氨基酚代谢物的有效分离。结果表明，所提出的2D-LC方法在治疗药物分析和药代动力学研究中具有很大的潜力。

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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.