{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T16:27:00Z","timestamp":1778344020836,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2023,9,30]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Baricitinib (BARI), an inhibitor of Janus kinases 1 and 2 (JAK 1\/2), is used for the treatment of rheumatoid arthritis and COVID\u201019. The present study focuses on establishing the forced degradation behavior of BARI under different degradation conditions (hydrolysis, oxidation, and photolysis) following International Council for Harmonization (ICH)\u00a0guidelines of Q1A (R2)\u2014Stability testing of new drug substances and products and Q1B\u2014Photostability testing of new drug substances and products. This study helps in monitoring the quality and safety of BARI and its product development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prior to conducting the study, the in silico degradation profile of BARI was predicted by Zeneth. Reversed\u2010phase high\u2010performance liquid chromatography employing a gradient program was used for the identification and separation of degradation impurities with an InertSustain C8 column (4.6\u2009\u00d7\u2009250\u2009mm, 5\u00a0\u03bcm). The mobile phases used were 10\u2009mM ammonium formate (pH\u20092.89) and acetonitrile. High\u2010resolution mass spectrometry (HRMS) was used for the structural elucidation of the degradation impurities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BARI was labile to hydrolytic (acidic, basic, and neutral) and photolytic degradation conditions which yielded 10 new degradation impurities and it was stable under oxidative (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) conditions. The separated degradation impurities were characterized by HRMS and the respective degradation pathways were proposed. The generated information helped to propose a mechanism for the formation of the degradation impurities. Additionally, one\u2010dimensional and two\u2010dimensional nuclear magnetic resonance spectroscopy were used for the characterization of two major degradation impurities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The forced degradation study of BARI was carried out in accordance with ICH Q1A and Q1B guidelines, which resulted in the formation of 10 new degradation impurities. In our analysis, three degradation impurities were matching with the Zeneth predictions. In silico tools, DEREK Nexus\u00ae and SARAH Nexus\u00ae, were used for predicting the toxicity and mutagenicity of BARI and its degradation impurities. Overall, this study sheds light on BARI's safety monitoring and storage circumstances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.9605","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T19:58:15Z","timestamp":1691438295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Forced degradation study of baricitinib and structural characterization of its degradation impurities by high\u2010resolution mass spectrometry and nuclear magnetic resonance spectroscopy"],"prefix":"10.1002","volume":"37","author":[{"given":"Sowmya","family":"Chaganti","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek","family":"Dhiman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya","family":"Madhyanapu Golla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshitha","family":"K R","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Khemchandani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2013.05.006"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"1","article-title":"A review on stress testing of drug substances and drug product","volume":"2013","author":"Musmade DS","year":"2012","journal-title":"Inven Rapid Pharm Process Dev"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01510"},{"issue":"4","key":"e_1_2_11_5_1","first-page":"694","article-title":"The effect of JAK1\/JAK2 inhibition in rheumatoid arthritis: efficacy and safety of baricitinib","volume":"37","author":"Choy EH","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_11_6_1","unstructured":"EMA.Olumiant. 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