{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:07:47Z","timestamp":1790690867843,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ivosidenib (Tibsovo) is a groundbreaking, first\u2010in\u2010class medication that specifically and reversibly blocks isocitrate dehydrogenase (IDH1), earning multiple FDA approvals for cancers harboring IDH1 mutations. This research developed a rapid, dependable, and sensitive UPLC\u2010MS\/MS technique to assess the metabolic stability of ivosidenib (IVB) in human liver microsomes (HLM). The method showed a commendable environmental profile (ComplexMoGAPI score: 69.0, AGREEprep: 0.68, and AGSA: 72.22). Using StarDrop software (including DEREK and P450 tools), chemical structure alerts were detected, and in silico analysis of metabolic vulnerability (CSL value) was conducted. A straightforward isocratic mobile phase system with a stationary phase (C8 column) efficiently separated IVB and baricitinib (BCB as internal standard) in an ultra\u2010fast 1\u2010min run at 0.4\u2009ml\/min flow rate. The IVB calibration curve showed a linearity over the range 1.0 to 4000\u2009ng\/ml. Accuracy and precision during intra\u2010 and inter\u2010day assessments in the range of \u22122.18% to 10.17% and \u22122.83% to 12.50%, respectively. The current approach uniquely combines HLMs\u2010based metabolic stability assessment with in silico predictions of metabolic soft spots, toxicity, and ADME, along with dual greenness evaluation, all within a single workflow. The in vitro half\u2010life (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) of IVB was approximately 44.89\u2009min, with an intrinsic clearance (Cl\n                    <jats:sub>int<\/jats:sub>\n                    ) of 18.06\u2009ml\/min\/kg. In silico analysis suggests that IVB derivatives with modifications to the 5\u2010fluoro\u20103\u2010pyridine group (75% at C21) and the 4\u2010cyano\u20102\u2010pyridine group (23% at C36) may exhibit varying metabolic stability, warranting further experimental validation.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70331","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:13:07Z","timestamp":1789485187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Ultra\u2010Fast UPLC\u2010MS\/MS Method for Quantifying Ivosidenib: Application to Assessment of Metabolic Stability in Human Liver Microsomes"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-4960","authenticated-orcid":false,"given":"Mohamed W.","family":"Attwa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry College of Pharmacy Riyadh 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