Abstract：
The study aimed to analyze nusinersen metabolites in the cerebrospinal fluid samples using ion-pair reversed-phase ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Three different sample preparation methods were tested for extraction and purification, but solid phase extraction appeared to be the most suitable, allowing a significant sample enrichment (40-fold). This step was necessary to detect and identify metabolites of nusinersen in the cerebrospinal fluid. The developed and applied analytical procedure enabled the identification of nusinersen metabolites: sequences shorter by several nucleotides from the 3\' end; shorter by several nucleotides from both the 3\' and 5\' ends; and some depurination products. To the best of our knowledge, this is the first report on the analysis and identification of nusinersen metabolites in cerebrospinal fluid samples taken from children with spinal muscular atrophy treated with Spinraza.
摘要：
该研究旨在使用离子对反相高效液相色谱结合四极杆飞行时间质谱分析脑脊液样品中的nusinersen代谢物。测试了三种不同的样品制备方法的提取和纯化，但是固相萃取似乎是最合适的，允许显著的样品富集（40倍）。此步骤对于检测和鉴定脑脊液中nusinersen的代谢物是必要的。开发和应用的分析程序能够鉴定nusinersen代谢物：从3'端缩短几个核苷酸的序列；从3'和5'端缩短几个核苷酸；和一些脱嘌呤产物。据我们所知,这是对Spinraza治疗的脊髓性肌萎缩症患儿脑脊液样本中nusinersen代谢物的分析和鉴定的第一份报告.
