一种用于定量测定脑脊液中硫酸皮肤素作为黏多糖贮积症II生物标志物的新型液相色谱-串联质谱分析法。
A novel LC-MS/MS assay to quantify dermatan sulfate in cerebrospinal fluid as a biomarker for mucopolysaccharidosis II.
作者信息
Pan Peng, Chen Mu, Zhang Zhiling, Corte Amauri Dalla, Souza Carolina, Giugliani Roberto, Pan Luying, Qiu Yongchang, Amaravadi Lakshmi, Wu Jiang
机构信息
Shire, 300 Shire Way, Lexington, MA 02421, USA.
Frontage Laboratories, Inc., 700 Pennsylvania Drive, Exton, PA 19341, USA.
出版信息
Bioanalysis. 2018 Jun 1;10(11):825-838. doi: 10.4155/bio-2018-0025. Epub 2018 Jun 4.
AIM
The study aimed to develop an LC-MS/MS assay to measure dermatan sulfate (DS) in human cerebrospinal fluid (CSF).
METHODS & RESULTS: DS was quantified by ion pairing LC-MS/MS analysis of the major disaccharides derived from chondroitinase B digestion. Artificial CSF was utilized as a surrogate for calibration curve preparation. The assay was fully validated, with a linear range of 20.0-4000 ng/ml, accuracy within ±20%, and precision of ≤20%. CSF samples from mucopolysaccharidoses (MPS) II patients showed an average of 11-fold increase in DS levels compared with controls.
CONCLUSION
The described assay is capable of differentiating DS levels in the CSF of MPS II patients from controls and can be used to monitor disease progression and therapeutic responses.
目的
本研究旨在开发一种液相色谱-串联质谱（LC-MS/MS）测定法，用于测量人脑脊液（CSF）中的硫酸皮肤素（DS）。
方法与结果
通过对软骨素酶B消化产生的主要二糖进行离子对LC-MS/MS分析来定量DS。使用人工脑脊液作为制备校准曲线的替代物。该测定法经过全面验证，线性范围为20.0 - 4000 ng/ml，准确度在±20%以内，精密度≤20%。与对照组相比，黏多糖贮积症（MPS）II型患者的脑脊液样本中DS水平平均升高了11倍。
结论
所描述的测定法能够区分MPS II型患者脑脊液中的DS水平与对照组，可用于监测疾病进展和治疗反应。
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