Authors
Julianne L Holleran, Joshua J Deppas, Ye Feng, Michael J Hochman, Evan C Chen, Maximilian Stahl, Steven D Gore, Timothy W Synold, Jan H Beumer, Raman Venkataramanan, Robert A Parise
Published in
Biomedical chromatography : BMC. Volume 40. Issue 10. Pages e70565.
Abstract
CDC-like kinases (CLK) and dual-specificity tyrosine-regulated kinases (DYRK) are protein kinases involved in various cellular functions, mRNA splicing, and DNA damage repair. CLK/DYRK kinases have been implicated in many disorders such as diabetes, neurodegenerative diseases, and cancer. Cirtuvivint (SM08502) is an orally bioavailable, first-in-class pan-CLK and pan-DYRK inhibitor that modulates pre-mRNA splicing and has shown the ability to inhibit cancer cell growth in vitro and reduce tumor burden in vivo. This has led to the administration of cirtuvivint in phase I clinical trials. To quantitate cirtuvivint, we have developed and validated an LC-MS/MS method in human plasma. The assay is simple and robust and consists of a protein precipitation, dilute-and-shoot extraction method using 20 μL of plasma, chromatographic separation with a Phenomenex Kinetex C18, and a gradient mobile phase system consisting of 0.1% formic acid in water and acetonitrile. The chromatographic method is followed by mass spectrometric detection with a SCIEX 4500 tandem mass spectrometer. The method has a 5-min run time and is linear from 5 to 1000 ng/mL. The assay met the criteria outlined by the US Food and Drug Administration guidance for bioanalytical method validation and will support ongoing and future clinical studies defining cirtuvivint pharmacokinetics.
PMID:
42610493
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.
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