INTRODUCTION Standardized commercial kits enable targeted metabolomics analysis and may thus provide an attractive complement to the more explorative approaches. The kits are typically developed for triple quadrupole mass spectrometers using serum and plasma. OBJECTIVES Here we measure the concentrations of preselected metabolites in cerebrospinal fluid (CSF) using a kit developed for high-resolution mass spectrometry (HRMS). Secondarily, the study aimed to investigate metabolite alterations in patients with secondary progressive multiple sclerosis (SPMS) compared to controls. METHODS We performed targeted metabolomics in human CSF on twelve SPMS patients and twelve age and sex-matched healthy controls using the Absolute IDQ-p400 kit (Biocrates Life Sciences AG) developed for HRMS. The extracts were analysed using two methods; liquid chromatography-mass spectrometry (LC-HRMS) and flow injection analysis-MS (FIA-HRMS). RESULTS Out of 408 targeted metabolites, 196 (48%) were detected above limit of detection and 35 were absolutely quantified. Metabolites analyzed using LC-HRMS had a median coefficient of variation (CV) of 3% and 2.5% between reinjections the same day and after prolonged storage, respectively. The corresponding results for the FIA-HRMS were a median CV of 27% and 21%, respectively. We found significantly (p < 0.05) elevated levels of glycine, asymmetric dimethylarginine (ADMA), glycerophospholipid PC-O (34:0) and sum of hexoses in SPMS patients compared to controls. CONCLUSION The Absolute IDQ-p400 kit could successfully be used for quantifying targeted metabolites in the CSF. Metabolites quantified using LC-HRMS showed superior reproducibility compared to FIA-HRMS.

中文翻译：

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使用高分辨率质谱在健康个体和继发进行性多发性硬化症患者中脑脊液的目标代谢组学。

简介标准化的商业试剂盒可进行靶向代谢组学分析，因此可为更具探索性的方法提供有吸引力的补充。该套件通常是为使用血清和血浆的三重四极杆质谱仪开发的。目的在这里，我们使用为高分辨率质谱（HRMS）开发的试剂盒来测量脑脊液（CSF）中预选代谢物的浓度。其次，该研究旨在研究继发性进行性多发性硬化症（SPMS）患者与对照组相比代谢产物的变化。方法我们使用为HRMS开发的Absolute IDQ-p400试剂盒（Biocrates Life Sciences AG），对12名SPMS患者和12名年龄和性别匹配的健康对照进行了人类CSF靶向代谢组学研究。使用两种方法分析提取物；液相色谱-质谱（LC-HRMS）和流动注射分析-MS（FIA-HRMS）。结果在408种目标代谢产物中，有196种（48％）被检测出检测限以上，并且有35种被绝对定量。使用LC-HRMS分析的代谢物在同一天和延长储存后的两次进样之间的中位变异系数（CV）分别为3％和2.5％。FIA-HRMS的相应结果分别为CV中值27％和21％。我们发现与对照组相比，SPMS患者的甘氨酸，不对称二甲基精氨酸（ADMA），甘油磷脂PC-O（34：0）和己糖总和水平显着（p <0.05）升高。结论Absolute IDQ-p400试剂盒可成功用于定量CSF中的目标代谢物。