{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:07:01Z","timestamp":1789661221849,"version":"4.0.1"},"reference-count":11,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["BC210533"],"award-info":[{"award-number":["BC210533"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["BC211396"],"award-info":[{"award-number":["BC211396"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA230972"],"award-info":[{"award-number":["CA230972"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["BC240179"],"award-info":[{"award-number":["BC240179"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>CDC\u2010like kinases (CLK) and dual\u2010specificity tyrosine\u2010regulated 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\u2010in\u2010class pan\u2010CLK and pan\u2010DYRK inhibitor that modulates pre\u2010mRNA splicing and has shown the ability to inhibit cancer cell growth in\u00a0vitro and reduce tumor burden in\u00a0vivo. This has led to the administration of cirtuvivint in phase I clinical trials. To quantitate cirtuvivint, we have developed and validated an LC\u2013MS\/MS method in human plasma. The assay is simple and robust and consists of a protein precipitation, dilute\u2010and\u2010shoot extraction method using 20\u2009\u03bcL 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\u2010min run time and is linear from 5 to 1000\u2009ng\/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.<\/jats:p>","DOI":"10.1002\/bmc.70565","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:30:14Z","timestamp":1787049014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitation of Cirtuvivint (SM08502) in Human Plasma by LC\u2013MS\/MS"],"prefix":"10.1002","volume":"40","author":[{"given":"Julianne L.","family":"Holleran","sequence":"first","affiliation":[{"name":"Cancer Therapeutics Program UPMC Hillman Cancer Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9093-7459","authenticated-orcid":false,"given":"Joshua J.","family":"Deppas","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program UPMC Hillman Cancer Center  Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer Center  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0594-154X","authenticated-orcid":false,"given":"Michael J.","family":"Hochman","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-5901","authenticated-orcid":false,"given":"Maximilian","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Medical Oncology and Hematology Yale University School of Medicine and Yale Comprehensive Cancer Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Gore","sequence":"additional","affiliation":[{"name":"Division of Cancer Treatment and Diagnosis, Investigational Drug Branch, Cancer Therapy Evaluation Program National Cancer Institute  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-2544","authenticated-orcid":false,"given":"Timothy W.","family":"Synold","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer Center  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8978-9401","authenticated-orcid":false,"given":"Jan H.","family":"Beumer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Oncology and Division of Clinical Pharmacology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-3290","authenticated-orcid":false,"given":"Raman","family":"Venkataramanan","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program UPMC Hillman Cancer Center  Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Pathology, School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-6271","authenticated-orcid":false,"given":"Robert A.","family":"Parise","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program UPMC Hillman Cancer Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"2002. \u201cCommission Decision (2002\/657\/EC) of 12 August 2002 Implementing Council Directive 96\/23\/EC Concerning the Performance of Analytical Methods and the Interpretation of Results.\u201d OJ L 221 17.8.2002 8\u201336. Brussels Belgium."},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","unstructured":"Corr B. R. M. R.Moroney E.Woodruff et\u00a0al.2023. \u201cCombination CDC\u2010Like Kinase Inhibition (CLK)\/Dual\u2010Specificity Tyrosine\u2010Regulated Kinase (DYRK) and Taxane Therapy in CTNNB1\u2010Mutated Endometrial Cancer.\u201d bioRxiv.https:\/\/doi.org\/10.1101\/2023.04.04.535570.","DOI":"10.1101\/2023.04.04.535570"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.02.011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","unstructured":"Naqvi A. S. P. J.Sullivan R. J.Corbett et\u00a0al.2025. \u201cCharacterization of Aberrant Splicing in Pediatric Central Nervous System Tumors Reveals CLK1 as a Candidate Oncogenic Dependency.\u201d bioRxiv.https:\/\/doi.org\/10.1101\/2024.08.03.606419.","DOI":"10.1101\/2024.08.03.606419"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1081\/jlc\u2010100101455"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001409\u20104"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.09.009"},{"key":"e_1_2_8_9_1","volume-title":"Guidance for Industry\u2010Bioanalytical Method Validation","author":"U.S. Department of Health and Human Services Food and Drug Administration","year":"2018"},{"key":"e_1_2_8_10_1","volume-title":"Guidance for Industry\u2010M10 BIOANALYTICAL METHOD VALIDATION AND STUDY SAMPLE ANALYSIS","author":"U.S. Department of Health and Human Services Food and Drug Administration","year":"2022"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.13728"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.05.031"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70565","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.70565","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70565","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:31:19Z","timestamp":1789659079000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":11,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bmc.70565"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70565","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2026-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70565"}}