{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:03:06Z","timestamp":1780380186167,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"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":[[2022,11,30]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Metabolite profiling is an integral part of the drug development process for selecting candidates with high therapeutic efficacy and low risk. Baricitinib (BARI) was approved in 2018 by the US Food and Drug Administration to treat rheumatoid arthritis. According to the available literature, no systematic study has been reported on the metabolite profiling of BARI. The biotransformation pathway of the drug has also not been established until recently. This study aims to identify BARI metabolites generated in in vitro matrices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The in vitro metabolism study was carried out using rat liver microsome, human liver microsomes, and human S9 fraction. Ultra high\u2010performance liquid chromatography quadrupole time\u2010of\u2010flight tandem mass spectrometry (U\u2010HPLC\u2010Q\/TOF) and ultra\u2010high\u2010performance liquid chromatography\/linear ion trap\u2010Orbitrap mass spectrometry (U\u2010HPLC\/LTQ\u2010Orbitrap\u2010MS\/MS) were used to identify and characterize the metabolites of BARI. The in silico toxicity of BARI and its metabolite was studied using ProTox\u2010II toxicity predictor software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of five new metabolites have been identified amongst which two (M1 and M2) were detected on both U\u2010HPLC\/LTQ\u2010Orbitrap\u2010MS\/MS and U\u2010HPLC\u2010Q\/TOF and two additional metabolites (M4 and M5) were detected on U\u2010HPLC\/LTQ\u2010Orbitrap\u2010MS\/MS. Moreover, one metabolite (M3) was only detected on LC\u2010QTOF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The major metabolic changes were found to be N\u2010dealkylation, demethylation, hydroxylation, and hydrolysis. Metabolites M3 and M4 were found to have the potential for carcinogenicity. The novelty of the study can be justified by the unavailability of any previous research on in vitro metabolite profiling of BARI. Furthermore, this is the first time the biotransformation pathway of BARI and the toxicity potential of its metabolites have been reported.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.9385","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T13:39:00Z","timestamp":1661521140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["High resolution mass spectrometry\u2010driven metabolite profiling of baricitinib to report its unknown metabolites and step\u2010by\u2010step reaction mechanism of metabolism"],"prefix":"10.1002","volume":"36","author":[{"given":"Megha","family":"Rachmale","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj","family":"Rajput","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarang","family":"Jadav","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit Kumar","family":"Sahu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyasheel","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Natural Products, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-7057","authenticated-orcid":false,"given":"Pinaki","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research\u2010Ahmedabad An Institute of National Importance, Government of India, Opp. Airforce Station, Palaj  Gandhinagar Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to 8.4 Years: An Updated Integrated Safety Analysis","author":"Genovese M","year":"2020"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2017.1359256"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010020\u201000938\u2010z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.04.017"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25071600"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3797\/scipharm.1510\u201008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.22270\/jddt.v9i4\u2010s.3230"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.354"},{"key":"e_1_2_8_11_1","unstructured":"https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/207924s000lbl.pdf"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.08.013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2020.122142"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2018.08.019"},{"key":"e_1_2_8_15_1","first-page":"59","article-title":"In vitro and in vivo metabolic investigation of the palbociclib by UHPLC\u2010Q\u2010TOF\/MS\/MS and in silico toxicity studies of its metabolites","volume":"157","author":"Chavan BB","year":"2018","journal-title":"J Chromatogr B"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmaa044"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5082"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.3640"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2021.123011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.114753"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2015.1086781"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.009241"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.9385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rcm.9385","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.9385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T11:44:58Z","timestamp":1761479098000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.9385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":21,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2022,11,30]]}},"alternative-id":["10.1002\/rcm.9385"],"URL":"https:\/\/doi.org\/10.1002\/rcm.9385","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/RCM.9385\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/RCM.9385\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/RCM.9385\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/RCM.9385\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/RCM.9385\/v1\/review1","asserted-by":"object"}]},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"value":"0951-4198","type":"print"},{"value":"1097-0231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]},"assertion":[{"value":"2022-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e9385"}}