{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:34:50Z","timestamp":1789598090923,"version":"build-2803163510"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Therapeutic drug monitoring (TDM) using cyclin-dependent kinase inhibitors (CDK4\/6is) is a novel approach for optimizing treatment outcomes. Currently, palbociclib, ribociclib, and abemaciclib are the available CDK4\/6is and are primarily coadministered with letrozole. This study aimed to develop and validate an LC-MS\/MS method for the simultaneous analysis of CDK4\/6is, 2 active metabolites of abemaciclib (M2 and M20), and letrozole in human plasma for use in TDM studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Sample pretreatment comprised protein precipitation with methanol and dilution of the supernatant with an aqueous mobile phase. Chromatographic separation was achieved using a reversed-phase XBridge BEH C18 column (2.5 \u03bcm, 3.0 \u00d7 75 mm XP), with methanol serving as the organic mobile phase and pyrrolidine\u2013pyrrolidinium formate (0.005:0.005 mol\/L) buffer (pH 11.3) as the aqueous mobile phase. A triple quadrupole mass spectrometer was used for the detection, with the ESI source switched from negative to positive ionization mode and the acquisition performed in multiple reaction monitoring mode.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>The complete validation procedure was successfully performed in accordance with the latest regulatory guidelines. The following analytical ranges (ng\/mL) were established for the tested compounds: 6\u2013300, palbociclib and letrozole; 120\u20136000, ribociclib; 40\u2013800, abemaciclib; and 20\u2013400, M2 and M20. All results met the acceptance criteria for linearity, accuracy, precision, selectivity, sensitivity, matrix effects, and carryover. A total of 85 patient samples were analyzed, and all measured concentrations were within the validated ranges. The percent difference for the reanalyzed samples ranged from \u221211.2% to 7.0%.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A simple and robust LC-MS\/MS method was successfully validated for the simultaneous quantification of CDK4\/6is, M2, M20, and letrozole in human plasma. The assay was found to be suitable for measuring steady-state trough concentrations of the analytes in patient samples.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001174","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T05:00:43Z","timestamp":1708146043000},"page":"485-493","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic Monitoring of Palbociclib, Ribociclib, Abemaciclib, M2, M20, and Letrozole in Human Plasma: A Novel LC-MS\/MS Method"],"prefix":"10.1097","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-8827","authenticated-orcid":false,"given":"Bianca","family":"Posocco","sequence":"first","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Zanchetta","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Orleni","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gagno","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Montico","sequence":"additional","affiliation":[{"name":"Clinical Trial Office, Scientific Direction-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Roncato","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"},{"name":"Department of Medicine, University of Udine, Udine, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gerratana","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Corsetti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, Udine, Italy; and"},{"name":"Department of Medical Oncology-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Toffoli","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology Unit-CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"R4-20250603","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1093\/jnci\/djaa071","article-title":"Overall survival of CDK4\/6-inhibitor\u2013based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and 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