心血管疾病的靶向代谢组学：高通量HPLC-MS/MS分析的验证

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-07-09 DOI:10.1016/j.jchromb.2025.124732

Sabina N. Baskhanova , Natalia E. Moskaleva , Ksenia M. Shestakova , Maria V. Kozhevnikova , Ekaterina O. Korobkova , Victor M. Samoylov , Svetlana A. Appolonova

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引用次数: 0

摘要

心血管疾病（CVD）仍然是世界范围内死亡的主要原因，需要创新的诊断工具来改进早期发现和管理。本研究优化并验证了一种高通量HPLC-MS/MS方法，用于同时定量人血浆中98种代谢物，包括氨基酸及其衍生物（n = 29）、色氨酸途径代谢物（n = 17）、核苷（n = 4）、水溶性维生素（n = 3）、酰基肉碱（n = 39）和其他代谢物（n = 6）。该方法利用化学衍生化来提高极性代谢物的保留率和灵敏度，提供跨不同物理化学性质的准确分析。该方法按照EMA指南进行了验证，包括线性度、准确度、精密度、基质效应、回收率和稳定性的评估。平行度测试证实了替代矩阵校准的适用性。该方法用于分析399名心血管疾病患者和75名健康对照者的血浆样本，揭示了与炎症、一氧化氮代谢和线粒体功能相关的途径的显着代谢改变。所提出的综合方法可以作为一种快速筛选方法，用于鉴定选择性CVD生物标志物，使用靶向代谢组学分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Targeted metabolomics for cardiovascular disease: Validation of a high-throughput HPLC-MS/MS assay

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Targeted metabolomics for cardiovascular disease: Validation of a high-throughput HPLC-MS/MS assay

Cardiovascular diseases (CVD) remain a leading cause of mortality worldwide, necessitating innovative diagnostic tools to improve early detection and management. This study represents the optimization and validation of a high-throughput HPLC-MS/MS method for simultaneous quantification of 98 metabolites in human plasma, including amino acids and its derivatives (n = 29), tryptophan pathway metabolites (n = 17), nucleosides (n = 4), water-soluble vitamins (n = 3), acylcarnitines (n = 39), and others (n = 6). The method utilizes chemical derivatization to enhance retention and sensitivity of polar metabolites providing accurate analysis across diverse physicochemical properties. The presented method was validated in accordance with EMA guidelines and included assessment of linearity, accuracy, precision, matrix effects, recovery, and stability. Parallelism testing confirmed the suitability of a surrogate matrix for calibration. The method was applied for the analysis of plasma samples from 399 patients with cardiovascular diseases and 75 healthy controls, revealing significant metabolic alterations in pathways associated with inflammation, nitric oxide metabolism, and mitochondrial function. The presented comprehensive approach may serve as a rapid screening method for the identification of selective CVD biomarkers using targeted metabolomic profiling.

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.