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

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research 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

Abstract

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.

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。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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