开发并验证测定人血清和脑脊液中可溶性斥导分子 A 的超高效液相色谱-串联质谱法。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-10 DOI:10.1080/17576180.2024.2403241
Patrick Schreier, Lili Huang, Emma Fung, Jennifer Mollon, Bernhard Sielaff, Marc R Lake, Michael Schulz, Khader Awwad
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引用次数: 0

摘要

目的:神经退行性疾病会导致斥导分子A(RGMa)上调。为了评估人血清和脑脊液(CSF)中的 RGMa 水平,我们根据 ICH M10 指南开发并验证了一种定量方法:样品制备包括免疫沉淀(IP,仅适用于血清)、消化和纯化,然后进行质谱分析:建立了一种UPLC-MS/MS方法,用于评估健康对照组、轻度认知障碍或阿尔茨海默病患者血清和脑脊液中可溶性RGMa水平的正常范围。健康对照组的正常范围为 13.0-44.8 纳克/毫升(脑脊液)和 9.9-20.9 纳克/毫升(血清)。在轻度认知障碍和阿尔茨海默病患者的脑脊液中,可溶性 RGMa 总量降低了两倍,而在血清中则保持不变。
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Development and validation of an ultra-performance liquid chromatography with tandem mass spectrometry method for determination of soluble repulsive guidance molecule A in human serum and cerebrospinal fluid.

Aim: Repulsive guidance molecule A (RGMa) is upregulated in neurodegenerative diseases. To assess RGMa levels in human serum and cerebrospinal fluid (CSF), a quantification method was developed and validated according to ICH M10 guideline.Methods & results: Sample preparation consisted of immunoprecipitation (IP, only for serum), digestion and purification followed by MS.Conclusion: An UPLC-MS/MS method was established and used to assess normal range of soluble RGMa levels in serum and CSF of healthy controls, and patients with mild cognitive impairment or Alzheimer's disease. The normal range was between 13.0-44.8 ng/ml (CSF) and 9.9-20.9 ng/ml (serum) in healthy controls. In the CSF of patients with mild cognitive impairment and Alzheimer's disease, total soluble RGMa was twofold lower while unchanged in serum.

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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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