{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:16Z","timestamp":1785414436454,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["ORF-2026-754"],"award-info":[{"award-number":["ORF-2026-754"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ORF-2026-754"],"award-info":[{"award-number":["ORF-2026-754"]}],"id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Abemaciclib (ABM) in combination with tamoxifen (TAM) is an extremely significant treatment regimen for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. It is approved for patients to reduce the risk of cancer recurrence. A bioanalytical method for the simultaneous determination of this new anti-breast cancer combination and its pharmacokinetic application has not yet been reported. Methods: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC\u2013MS\/MS) method was developed for quantifying ABM, TAM, and its metabolites, including abemaciclib active metabolites M2, M18, and M20 and tamoxifen active metabolite N-desmethyl tamoxifen (NDTAM), in rat plasma using econazole as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 column (100 \u00d7 2.1 mm ID, 2.6 \u00b5m) using gradient elution with 5 mM ammonium formate in water (eluent A) and 5 mM ammonium formate in water\/methanol (1:9, v\/v, eluent B) at a flow rate of 0.4 mL\/min. Detection was performed on a TSQ Fortis Plus mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. Results: The developed method was validated according to the guidance of the FDA. Linearity in rat plasma (ng\/mL) was achieved from 1 to 1000 for ABM, TAM, and M20; 3 to 1000 for M2; 5 to 500 for M18; and 1 to 500 for NDTAM; with correlation coefficients ranging from 0.9991 to 0.9931 for all analytes using a weighting factor of 1\/X2. The lower limit of detection (LLOD) ranged between 0.3 and 1.5 ng\/mL for all drugs. The accuracy ranged from 96 to 108% and the precision was less than 7.6% RSD for all analytes. For the first time, the newly developed approach was effectively used in a pharmacokinetic study on the simultaneous oral administration of ABM and TAM in rats that received 30.0 mg\/kg of ABM and 8.0 mg\/kg of TAM. Conclusions: To the best of our knowledge, this is the first reported UPLC\u2013MS\/MS method for the assay of ABM, TAM, and its active metabolites in plasma. This method offers a bioanalytical tool for assessing the pharmacokinetics of ABM and TAM. Therefore, this study makes a definite significant contribution to the field of bioanalytical research. Further validation in human plasma is required for future clinical or therapeutic drug monitoring applications, as the approach was developed in an animal model.<\/jats:p>","DOI":"10.3390\/ph19050795","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:32:28Z","timestamp":1779676348000},"page":"795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Application of an UPLC\u2013MS\/MS Method for Simultaneous Quantification of Abemaciclib and Tamoxifen with Their Active Metabolites in Rat Plasma: Application to a Pharmacokinetic Study"],"prefix":"10.3390","volume":"19","author":[{"given":"Yahya","family":"Alshehri","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrhman","family":"Al-Majed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7532-6318","authenticated-orcid":false,"given":"Ahmad","family":"Obaidullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-4036","authenticated-orcid":false,"given":"Yousef","family":"Bin Jardan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bakheit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Hefnawy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 20). 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