{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:30:54Z","timestamp":1760059854625,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"],"award-info":[{"award-number":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kyung Hee University","award":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"],"award-info":[{"award-number":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"]}]},{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"],"award-info":[{"award-number":["23212MFDS228-1","20240967","21153MFDS601-1","RS-2024-00331810"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Selinexor is a selective nuclear-export inhibitor approved for hematologic malignancies, characterized by extensive plasma protein binding (&gt;95%). However, a validated analytical method to accurately measure the clinically relevant unbound fraction of selinexor in human plasma has not yet been established. This study aimed to develop a fully validated bioanalytical assay for simultaneous quantification of total and unbound selinexor concentrations in human plasma. Methods: We established and fully validated an analytical method based on liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) capable of quantifying total and unbound selinexor concentrations in human plasma. Unbound selinexor was separated using ultrafiltration, and selinexor was efficiently extracted from 50 \u03bcL of plasma by liquid\u2013liquid extraction. Chromatographic separation was achieved on a C18 column using an isocratic mobile phase (0.1% formic acid:methanol, 12:88 v\/v) with a relatively short runtime of 2.5 min. Results: Calibration curves showed excellent linearity over a range of 5\u20132000 ng\/mL for total selinexor (r2 \u2265 0.998) and 0.05\u201320 ng\/mL for unbound selinexor (r2 \u2265 0.995). The precision (%CV \u2264 10.35%) and accuracy (92.5\u2013104.3%) for both analytes met the regulatory criteria. This method successfully quantified selinexor in plasma samples from renally impaired patients with multiple myeloma, demonstrating potential inter-individual differences in unbound drug concentrations. Conclusions: This validated bioanalytical assay enables precise clinical pharmacokinetic assessments in a short runtime using a small plasma volume and, thus, assists in individualized dosing of selinexor, particularly for renally impaired patients with altered protein binding.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070919","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T13:00:51Z","timestamp":1752757251000},"page":"919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantification of Total and Unbound Selinexor Concentrations in Human Plasma by a Fully Validated Liquid Chromatography-Tandem Mass Spectrometry Method"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-4367","authenticated-orcid":false,"given":"Suhyun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju 55338, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seungwon","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0232-2618","authenticated-orcid":false,"given":"Hyeonji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-1386","authenticated-orcid":false,"given":"Wang-Seob","family":"Shim","sequence":"additional","affiliation":[{"name":"Kyung Hee Drug Analysis Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5927-7168","authenticated-orcid":false,"given":"Eunseo","family":"Song","sequence":"additional","affiliation":[{"name":"Kyung Hee Drug Analysis Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-5120","authenticated-orcid":false,"given":"Seunghoon","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Hematology Hospital, Seoul St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suein","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4674-7682","authenticated-orcid":false,"given":"Sungpil","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hwan","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7087-4914","authenticated-orcid":false,"given":"Seok Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beomjin","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-3727","authenticated-orcid":false,"given":"Kyung-Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Kyung Hee Drug Analysis Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-2799","authenticated-orcid":false,"given":"Eun Kyoung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Kyung Hee Drug Analysis Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/jha2.709","article-title":"Selinexor: Targeting a novel pathway in multiple myeloma","volume":"4","author":"Mo","year":"2023","journal-title":"eJhaem"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1177\/1060028019892643","article-title":"Selinexor: A First-in-Class Nuclear Export Inhibitor for Management of Multiply Relapsed Multiple Myeloma","volume":"54","author":"Peterson","year":"2020","journal-title":"Ann. 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