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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
LC-MS/MS quantification of nusinersen in rat cerebrospinal fluid and preclinical pharmacokinetics study application
Yujie Li1, Shu Zhang2, Xiayi Wang3
1School of Life Sciences, Qingdao Agricultural University, Qingdao, Shandong, China.
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.
