{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:12:14Z","timestamp":1790082734083,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ripretinib is an innovative multitargeted kinase inhibitor introduced for the treatment of advanced gastrointestinal stromal tumors, was investigated to elucidate its degradation behavior and structural transformation pathways under forced stress conditions. Although degradation studies are essential for evaluating the intrinsic stability of pharmaceutical compounds, the degradation products of ripretinib have not been comprehensively characterized. The present work focuses on LC\u2013HRMS\/MS\u2010based structural elucidation of degradation products arising from photolytic and hydrolytic stress conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In accordance with International Council for Harmonisation guidelines, ripretinib was subjected to acidic, alkaline, oxidative, thermal, and photolytic stress conditions. Liquid chromatography was employed to separate the degradation products, which were subsequently characterized by high\u2010resolution tandem mass spectrometry (LC\u2013HRMS\/MS) operated in positive electrospray ionization mode. Structural assignments were established using accurate mass measurements, isotopic pattern analysis, elemental composition determination, and collision\u2010induced dissociation pathways. Degradation kinetics under photolytic conditions were also evaluated. An\n                      <jats:italic>in silico<\/jats:italic>\n                      toxicity assessment of degradation products was performed using DEREK and SARAH prediction platforms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ripretinib exhibited degradation predominantly under photolytic and hydrolytic stress conditions, leading to the formation of five degradation products. The protonated molecule of ripretinib at\n                      <jats:italic>m\/z<\/jats:italic>\n                      510 displayed a characteristic bromine isotopic distribution that facilitated differentiation between brominated and debrominated products. Hydrolytic degradation generated two products through cleavage of the urea linkage, whereas photolytic degradation produced three products involving intramolecular cyclization with concomitant debromination, hydroxylation, and N\u2013C bond cleavage pathways. Collision\u2010induced dissociation of protonated molecules generated diagnostic product ions that enabled structural elucidation of all degradation products. Photodegradation followed apparent first\u2010order kinetics with a half\u2010life of 4.2\u2009min. One hydrolytic degradation product containing a primary aromatic amine moiety was predicted to possess mutagenic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This investigation elucidates the degradation pathways of ripretinib and highlights the utility of LC\u2013HRMS\/MS in the structural characterization of degradation products generated under stress conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70180","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:31:39Z","timestamp":1790080299000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LC\u2013HRMS\/MS Characterization of Hydrolytic and Photolytic Degradation Pathways of Ripretinib Following Forced Stress Studies"],"prefix":"10.1002","volume":"40","author":[{"given":"Vijaya Madhyanapu","family":"Golla","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"},{"name":"Analytical Research and Development Novartis Healthcare Pvt Ltd  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4590-2734","authenticated-orcid":false,"given":"Pushpa","family":"Pilli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhoopendra Singh","family":"Kushwah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"},{"name":"Analytical Research and Development Novartis Healthcare Pvt Ltd  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6611-1622","authenticated-orcid":false,"given":"Sowmya","family":"Chaganti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3474-7773","authenticated-orcid":false,"given":"Rahul","family":"Khemchandani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"},{"name":"Analytical Research and Development Novartis Healthcare Pvt Ltd  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6389-5994","authenticated-orcid":false,"given":"Gananadhamu","family":"Samanthula","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/crst.crst_308_20"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010022\u201001794\u20100"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2023.2167711"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon\u20102022\u20100226"},{"key":"e_1_2_11_6_1","first-page":"139","volume-title":"Handbook of Pharmaceutical Manufacturing Formulations","author":"Niazi S. 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