Development and Validation of an LC-MS/MS Assay for Quantitative Analysis of Nusinersen in Human CSF and Plasma
Tingting Xu1,2, Wei Zuo1,2, Zhuo Sun1,2
1Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Summary
A new method accurately measures nusinersen drug levels in spinal muscular atrophy (SMA) patients
Area of Science:
- Pharmacology
- Analytical Chemistry
- Biochemistry
Background:
- Nusinersen is a key treatment for spinal muscular atrophy (SMA).
- Pharmacokinetic data for nusinersen in Chinese SMA patients is currently unavailable.
- Accurate quantification methods are essential for therapeutic drug monitoring.
Purpose of the Study:
- To develop and validate a sensitive LC-MS/MS method for nusinersen quantification.
- To enable pharmacokinetic studies in Chinese SMA patient populations.
- To establish a reliable analytical tool for therapeutic drug monitoring.
Main Methods:
- Protein precipitation for sample preparation.
- Reversed-phase liquid chromatography (LC) using a C18 column.
- Tandem mass spectrometry (MS/MS) detection in negative ion MRM mode.
Main Results:
- The LC-MS/MS method was successfully validated for human plasma and cerebrospinal fluid (CSF).
- Quantification ranges were established: 5.00–1000 ng/mL for plasma and 2.00–400 ng/mL for CSF.
- This is the first reported LC-MS/MS quantification of nusinersen in human plasma and CSF.
Conclusions:
- A reliable and validated LC-MS/MS method for nusinersen quantification has been developed.
- This methodology will facilitate crucial pharmacokinetic studies in Chinese SMA patients.
- The method supports the clinical application of nusinersen in this population.