{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:55:47Z","timestamp":1791273347829,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"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":[[2026,12,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Fruquintinib (FRQ) is a recently approved drug for the treatment of metastatic colorectal cancer. To date, only a limited number of studies have investigated the stability\u2010indicating analysis of FRQ. Understanding its degradation pathways is essential for ensuring drug quality and safety, for regulatory compliance and for providing valuable insights into pharmaceutical development and quality control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FRQ was subjected to acid, base, oxidative, neutral, thermal, and photolytic stress as per ICH Q1A(R2). A stability\u2010indicating UPLC\u2010PDA method was developed on a Waters BEH C18 column (2.1\u2009\u00d7\u200950\u2009mm, 1.7\u2009\u03bcm) with gradient elution using a mobile phase of 10\u2009mM ammonium acetate (pH\u20093.5) and acetonitrile. Degradants were characterized by LTQ\u2010XL ion\u2010trap MS and LC\u2010QTOF\u2010MS\/MS, followed by silico ADMET prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The method is developed and validated in accordance with the ICH Q2(R2) guidelines. Forced degradation of FRQ under acidic, basic and oxidative stress conditions generated two common degradation products, DP\u20101 (\n                      <jats:italic>m<\/jats:italic>\n                      \/\n                      <jats:italic>z<\/jats:italic>\n                      207.0756) and DP\u20102 (\n                      <jats:italic>m<\/jats:italic>\n                      \/\n                      <jats:italic>z<\/jats:italic>\n                      221.0900), common to all three stress conditions, in addition to one degradation product specific to the oxidative pathway; FRQ was stable under neutral, thermal and photolytic conditions. The two major degradation products are identified and characterized by LC\u2010QTOF\u2010MS\/MS. Out of two DPs, the DP\u20102 product has not been reported previously. ADMET prediction indicated acceptable pharmacokinetic properties but flagged potential drug\u2013drug interaction risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The developed UPLC\u2010PDA method provides a robust stability\u2010indicating method for FRQ and enables comprehensive characterization of its degradation products. The discovery of the novel degradation product DP\u20102 expands current knowledge of FRQ degradation chemistry, whereas the combined analytical and in silico findings support pharmaceutical quality assessment, regulatory evaluation, and future safety investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70191","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:48:06Z","timestamp":1791272886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Validation of a Stability\u2010Indicating UPLC\u2010PDA Method for Fruquintinib: LC\u2010QTOF\u2010MS\/MS\u2010Based Structural Characterization of Degradation Products and\n                    <i>In Silico<\/i>\n                    ADMET Prediction"],"prefix":"10.1002","volume":"40","author":[{"given":"Shuvam","family":"Nayak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Quality Assurance Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal D.","family":"Labhade","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Quality Assurance Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhakti Umesh","family":"Hirlekar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-3926","authenticated-orcid":false,"given":"Shashank","family":"Tewari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-029X","authenticated-orcid":false,"given":"Sachin Dattram","family":"Pawar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Quality Assurance Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TRANON.2021.101174"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/CAAC.70067"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.32604\/OR.2025.067449"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20100281"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S215533"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010443\u201033885\u20104.00023\u20108"},{"key":"e_1_2_11_8_1","volume-title":"Stability Testing of New Drug Substances and Products Q1A(R2)","author":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals For Human Use ICH Harmonised Tripartite Guideline","year":"2003"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPHA.2013.09.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SCP.2026.102450"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2016.1242401"},{"key":"e_1_2_11_12_1","first-page":"1","volume-title":"Methods for Stability Testing of Pharmaceuticals, Methods in Methods in Pharmacology and Toxicology","author":"Singh D. 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