LC-MS/MS 方法直接测量人血浆中的sepiapterin 和四氢生物蝶呤及其临床应用。

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2024-01-01 Epub Date: 2023-12-15 DOI:10.4155/bio-2023-0144

Diksha Kaushik, Lan Gao, Kun Yuan, Bowen Tang, Ronald Kong

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引用次数: 0

摘要

目的：四氢生物蝶呤（BH4）是芳香族氨基酸羟化酶的天然辅助因子，sepiapterin 是 BH4 的天然前体，它们内源性地存在于人体血浆中。本文首次报道了通过 LC-MS/MS 直接定量检测人血浆中的 sepiapterin 和 BH4 的方法，用于药代动力学评估。材料与方法：血浆中的分析物取自经 10%抗坏血酸（AA）处理至最终浓度为 1%AA的血液。结果与结论：sepiapterin和BH4的定量方法的校准范围分别为0.75-500 ng/ml和0.5-500 ng/ml。由于分析物易发生氧化还原反应，因此定量具有挑战性。经过验证的方法已成功用于支持sepiapterin的临床开发。

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LC-MS/MS methods for direct measurement of sepiapterin and tetrahydrobiopterin in human plasma and clinical applications.

Aim: Tetrahydrobiopterin (BH₄), a natural cofactor of aromatic amino acid hydroxylases, and sepiapterin, a natural precursor of BH₄, are endogenously present in human plasma. This is the first report on methods for direct quantification of sepiapterin and BH₄ in human plasma by LC-MS/MS for pharmacokinetic assessment. Materials & methods: The analytes in plasma were harvested from blood that were treated with 10% ascorbic acid (AA) to a final concentration of 1% AA. Results & conclusion: The quantification methods were validated for calibration ranges of 0.75-500 ng/ml and 0.5-500 ng/ml for sepiapterin and BH₄, respectively. Quantification of analytes was challenging due to their susceptibility to redox reactions. The validated methods were utilized successfully to support clinical development of sepiapterin.

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.