大鼠脑脊液中nusinersen的LC-MS/MS定量及临床前药代动力学研究应用。

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2025-07-21 DOI:10.1080/17576180.2025.2535949

Yujie Li, Shu Zhang, Xiayi Wang, Xiaochuan Li, Lizhong Guo

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引用次数: 0

摘要

背景：nusinersen钠是一种用于治疗脊髓性肌萎缩症（SMA）的寡核苷酸药物，需要准确的检测才能进行治疗研究。液相色谱-串联质谱（LC-MS/MS）检测大鼠脑脊液（CSF）中nusinersen的方法尚未见报道。方法：建立并验证了hplc -MS/MS检测SD大鼠脑脊液中nusinersen的方法。方法采用固相萃取法进行萃取后分析，以dT20为内标。采用负离子多反应监测（MRM）模式扫描和电喷雾电离（ESI）源。该方法在5-2000 ng/mL的浓度范围内进行了验证，nusinersen的定量下限（LLOQ）为5 ng/mL。结果与结论：该方法具有极高的准确度和精密度，线性好，提取回收率高，可用于大鼠体内药代动力学评价。

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LC-MS/MS quantification of nusinersen in rat cerebrospinal fluid and preclinical pharmacokinetics study application.

Background: Background: An oligonucleotide drug named nusinersen sodium is used to treat Spinal Muscular Atrophy (SMA), requires accurate detection for therapeutic research. There are no published reports on liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting nusinersen in rat cerebrospinal fluid (CSF).

Methods: An LC-MS/MS method has been created and verified to detect nusinersen in Sprague-Dawley (SD) rat CSF. The method employed solid-phase extraction for post-extraction analysis and used dT20 as an internal standard. Negative ion multiple reaction monitoring (MRM) mode scanning and the electrospray ionization (ESI) source were used. The method was validated over a concentration range of 5-2000 ng/mL with a Lower Limit of Quantification (LLOQ) of for nusinersen at 5 ng/mL.

Results and conclusions: The method achieves extremely high accuracy and precision, good linearity, high extraction recovery, and provides a useful approach for evaluating the pharmacokinetics of nusinersen in rats.

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.