Cytochrome P450 (CYP450) pathway is one of the critical enzymatic via eicosanoid biosynthesis. Nevertheless, their metabolites are far less explored. This pathway plays a crucial role in converting arachidonic acid to hydroxyeicosatetraenoic (HETEs), epoxyeicosatrienoic (EETs), dihydroxyeicosatetraenoic acids (DiHETEs), and dihydroxyeicosatrienoic acids (DiHETrEs), which mediate several physiological and pathological functions. However, CYP450-derived eicosanoids are structurally complex, making those analyses a challenge in lipidomics studies. Herein, a high-resolution multiple-reaction monitoring (MRM^HR) method has been proposed as a powerful tool for the simultaneous analysis of CYP450-eicosanoids on different biological samples. The developed liquid chromatography (LC)-MRM^HR method was partially validated according to the Food and Drug Administration (FDA) criteria, demonstrating adequate specificity, linearity, precision, and accuracy. Besides, several biological samples were analyzed to guarantee the feasibility of the method. The proposed strategy may improve the understanding of CYP450-derived eicosanoids in biological systems, which could be fundamental to reveal new aspects of those in physiologic and pathologic conditions.

中文翻译：

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高分辨率多反应监测质谱法靶向分析细胞色素 P450 途径衍生的类花生酸

细胞色素 P450 (CYP450) 途径是通过类花生酸生物合成的关键酶之一。然而，它们的代谢物的探索却少得多。该途径在将花生四烯酸转化为羟基二十碳四烯酸 (HETEs)、环氧二十碳三烯酸 (EETs)、二羟基二十碳四烯酸 (DiHETEs) 和二羟基二十碳三烯酸 (DiHETrEs) 方面起着至关重要的作用，介导多种生理和病理功能。然而，CYP450 衍生的类二十烷酸结构复杂，使这些分析成为脂质组学研究的挑战。本文提出了一种高分辨率多反应监测 (MRM ^HR ) 方法作为同时分析不同生物样品上的 CYP450-类花生酸的有力工具。开发的液相色谱（LC）-MRM ^HR方法根据食品和药物管理局 (FDA) 标准进行了部分验证，证明了足够的特异性、线性、精密度和准确度。此外，还对多个生物样品进行了分析，以保证该方法的可行性。所提出的策略可能会提高对生物系统中 CYP450 衍生的类花生酸的理解，这可能是揭示生理和病理条件下新方面的基础。