{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:49:17Z","timestamp":1791982157500,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glasdegib (GSB) is an orally bioavailable Smoothened (Hedgehog pathway) inhibitor approved, in combination with low\u2010dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients who are unfit for intensive induction chemotherapy. Although GSB is predominantly cleared by hepatic CYP3A4\u2010mediated oxidation, no human liver microsomes (HLM) metabolic stability method has been reported; existing assays are limited to plasma matrices. Here, we describe an ultra\u2010fast validated UPLC\u2013MS\/MS method for GSB and apply it to the first assessment of metabolic stability in HLM. StarDrop WhichP450 (CSL\u2009=\u20090.8928) and DEREK alerts were performed to localize metabolic soft spots and safety liabilities. Chromatography was performed on an SB\u2010C18 column in 1\u2009min. The method was linear over 1\u20134000\u2009ng\/mL (\n                    <jats:italic>y<\/jats:italic>\n                    \u2009=\u20091.2753\n                    <jats:italic>x<\/jats:italic>\n                    \u2009+\u20090.4567;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.9992), with accuracy (\u22123.10 to +10.25 %E) and precision (\u2264\u20093.56 %RSD). GSB exhibited an in\u00a0vitro\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    of 44.15\u2009min and an intrinsic clearance of 18.37\u2009mL\/min\/kg (moderate\u2010clearance compound). The predicted soft spots (the N\u2010methylpiperidine ring [65%] and the benzimidazole moiety [29%]) are consistent with the known human N\u2010desmethyl metabolite and CYP3A4 dominance. The combined dataset provides a soft\u2010spot\u2010guided rationale for the metabolic optimization of future Hedgehog\u2010pathway inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70631","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:24:36Z","timestamp":1790864676000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A One\u2010Min, FDA\u2010Validated UPLC\u2013MS\/MS Method for the AML Smoothened Inhibitor Glasdegib Quantification and Metabolic Stability Assessment in Human Liver Microsomes: In Silico Metabolic Lability and Toxicity Screening"],"prefix":"10.1002","volume":"40","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 King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-5969","authenticated-orcid":false,"given":"Haitham","family":"AlRabiah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-1357","authenticated-orcid":false,"given":"Ahmed H.","family":"Bakheit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8115-4228","authenticated-orcid":false,"given":"Adnan A.","family":"Kadi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA03251G"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2023.105117"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AN01036E"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AY01035G"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AN01132A"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2ra02885a"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2024.107540"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70231"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.70111"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70252"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AN01155H"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D6AN00077K"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.70130"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201900818"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.03.037"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2019.04.001"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(24)15284-1"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010020\u201000929\u20108"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jaoacint\/qsaa006"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)38813-0"},{"key":"e_1_2_12_22_1","first-page":"115","volume-title":"Handbook of Analytical Separations","author":"Gonz\u00e1lez O.","year":"2020"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.37022\/jiaps.v10i1.650"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20102952(94)90520\u20107"},{"issue":"11","key":"e_1_2_12_25_1","first-page":"193","article-title":"Leukemia Perspective in Current Practice","volume":"20","author":"Karrari H. 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