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  3. Ultrasensitive Profiling of Arachidonic Acid Metabolites Based on 5‑(Diisopropylamino)amylamine Derivatization-Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry

Ultrasensitive Profiling of Arachidonic Acid Metabolites Based on 5‑(Diisopropylamino)amylamine Derivatization-Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry

  • ACS Pharmacol Transl Sci. 2025 Oct 4;8(11):4095-4106. doi: 10.1021/acsptsci.5c00498.
Peiyan Zheng 1 2 3 4,  Xiaowen Huang 1 5,  Qing Wang 1 2 3,  Yida Zhang 1 2 3,  Mingtao Liu 1 2 3,  Manyun Jiang 1 2 3,  Sitong Liu 1 2 3,  Huimin Huang 1 2 3,  Wenting Luo 1 2 3,  Jian-Lin Wu 4,  Baoqing Sun 1 2 3
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
  • 2 Guangzhou National Laboratory, Guangzhou 510005, China.
  • 3 Guangdong Provincial Clinical Research Center for Laboratory Medicine, Guangzhou 510080, China.
  • 4 State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China.
  • 5 Department of Respiratory, Zhongshan Boai Hospital, Zhongshan 528403, China.
PMID: 41262585 DOI: 10.1021/acsptsci.5c00498
Abstract

Arachidonic acid (AA) and its metabolites play critical roles in inflammation and immune regulation, modulating the initiation, amplification, and resolution of inflammation. However, their comprehensive quantification remains a challenging endeavor owing to complex metabolic pathways and biological matrix effects. This study introduces a novel metabolomics method involving 5-(diisopropylamino)-amylamine (DIAAA) derivatization coupled with ultraperformance liquid chromatography-tandem mass spectrometry to address these issues. The method demonstrated high sensitivity and specificity, with limits of quantification meeting stringent criteria (relative standard deviation <20%; recovery rate, 85-115%, signal-to-noise ratio >10). It effectively quantified 14 key AA metabolites, including hydroxyeicosatetraenoic acids, prostaglandins, and leukotrienes, across a wide linear range (R 2 > 0.98). The results of intra- and interassay precision tests exhibited low coefficients of variation (≤15%), underscoring the reproducibility of the method. DIAAA derivatization also mitigated matrix variability, improving the accuracy of metabolite detection in serum samples. The hallmark of allergic diseases is a disrupted AA metabolism, where elevated specific metabolites (AA, HETEs, LTB4, and PGD2) show strong diagnostic promise, and a unique metabolite signature in polysensitized patients indicates a link to inflammatory severity. This advanced analytical approach offers significant potential for elucidating the role of AA metabolism in allergic diseases and holds promise for applications in clinical diagnostics and therapeutic monitoring.

Keywords

5-(diisopropylamino)amylamine derivatization; arachidonic acid metabolites; metabolite quantification; ultraperformance liquid chromatography−tandem mass spectrometry.

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