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建立并验证超高效液相色谱-串联质谱法测定人血清和脑脊液中可溶性 repulsive guidance molecule A

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.

机构信息

AbbVie Deutschland GmbH & Co. KG, Knollstr., Rhineland-Palatinate, Ludwigshafen, 67061, Germany.

AbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.

出版信息

Bioanalysis. 2024;16(21-22):1155-1166. doi: 10.1080/17576180.2024.2403241. Epub 2024 Oct 10.

DOI:10.1080/17576180.2024.2403241
PMID:39387340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11583623/
Abstract

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. Sample preparation consisted of immunoprecipitation (IP, only for serum), digestion and purification followed by MS. 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.

摘要

repulsive guidance molecule A (RGMa) 在神经退行性疾病中上调。为了评估人血清和脑脊液 (CSF) 中的 RGMa 水平,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,仅用于血清)、消化和纯化,然后进行 MS。建立了 UPLC-MS/MS 方法,用于评估健康对照者血清和 CSF 中可溶性 RGMa 水平的正常范围,以及轻度认知障碍或阿尔茨海默病患者的正常范围。健康对照者的正常范围为 13.0-44.8ng/ml(CSF)和 9.9-20.9ng/ml(血清)。在轻度认知障碍和阿尔茨海默病患者的 CSF 中,总可溶性 RGMa 降低了一倍,而血清中未改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/4e9fcf692333/IBIO_A_2403241_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/f1faed179257/IBIO_A_2403241_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/743a8d8b7ec9/IBIO_A_2403241_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/4e9fcf692333/IBIO_A_2403241_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/f1faed179257/IBIO_A_2403241_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/743a8d8b7ec9/IBIO_A_2403241_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf0/11583623/4e9fcf692333/IBIO_A_2403241_F0003_C.jpg

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