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The objective of this study was to develop and validate a liquid chromatography coupled to tandem mass spectrometry (LC\u2013MS\/MS) methodology for quantifying nusinersen in human plasma and cerebrospinal fluid (CSF) samples. The samples were prepared by protein precipitation, and then the gradient was eluted on a column of Acquity UPLC Xbridge C18 by using acetonitrile with 0.5% triethylamine (TEA) and 0.5% hexafluoroisopropanol (HFIP) and water with 0.5% TEA and 0.5% HFIP as the mobile phase. Detection was performed on a QTRAP6500<jats:sup>+<\/jats:sup> tandem mass spectrometer in the negative ion multiple reaction monitoring (MRM) mode using electrospray ionization (ESI). The optimized method was successfully qualified for the nusinersen in human plasma and CSF samples over the range of 5.00 to 1000\u2009ng\/mL and 2.00 to 400\u2009ng\/mL, respectively. Importantly, our work is the first report of quantification of nusinersen in human plasma and CSF by LC\u2013MS\/MS methodology. The developed methodology is reliable and will be applied to PK study of nusinersen in Chinese SMA patients.<\/jats:p>","DOI":"10.1002\/bmc.70138","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T01:53:22Z","timestamp":1749866002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and Validation of an LC\u2013MS\/MS Assay for Quantitative Analysis of Nusinersen in Human CSF and Plasma"],"prefix":"10.1002","volume":"39","author":[{"given":"Tingting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6681-214X","authenticated-orcid":false,"given":"Simin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqing","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2643-0706","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.94"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13361\u2010017\u20101671\u20106"},{"key":"e_1_2_11_4_1","unstructured":"Biogen Inc. 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