{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:32:44Z","timestamp":1761514364168,"version":"build-2065373602"},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T00:00:00Z","timestamp":1557792000000},"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":[[2019,6,15]]},"abstract":"\n Rationale<\/jats:title>\n \n Brexpiprazole is a novel serotonin\u2013dopamine activity modulator approved by the USFDA in July 2015 for the treatment of schizophrenia and as an adjunctive therapy with other antidepressants for major depressive disorder in adults. However, limited numbers of metabolites are reported in the literature for brexpiprazole. Our prime intent behind this study is to revisit metabolite profiling of brexpiprazole and to identify and characterize all possible\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n metabolites.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Firstly, the site of metabolism for brexpiprazole was predicted by a Xenosite web predictor model. Secondly,\n in vitro<\/jats:italic>\n metabolite profiling was performed by incubating the drug individually with rat liver microsomes, human liver microsomes and rat S9 fraction at 37\u00b0C for 1\u2009h in incubator shaker. Finally, for\n in vivo<\/jats:italic>\n metabolite identification, a 50 mg\u2009kg\n \u22121<\/jats:sup>\n dose of brexpiprazole was administered to male Sprague\u2013Dawley rats and the presence of various metabolites was confirmed in rat plasma, urine and feces.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The predicted atomic site of metabolism was obtained as a color gradient by the Xenosite web predictor tool and, from this study, probable metabolites were listed. In total, 14 phase I and 2 phase II metabolites were identified and characterized in the\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n matrices using ultra\u2010high\u2010performance liquid chromatography\/quadrupole time\u2010of\u2010flight tandem mass spectrometry (UHPLC\/QTOF\u2010MS\/MS). The majority of metabolites were found in the sample incubated with human liver microsomes and in rat urine, while in the other matrices only a few metabolites were detected.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n All the 16 metabolites were identified and characterized using UHPLC\/QTOF\u2010MS\/MS. The study revealed that brexpiprazole is metabolized via hydroxylation, glucuronidation, S\u2010oxidation, N\u2010oxidation, dioxidation, oxidative deamination, N\u2010dealkylation, etc.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/rcm.8436","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:13:36Z","timestamp":1553040816000},"page":"1024-1035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In silico<\/i>\n ,\n in vitro<\/i>\n and\n in vivo<\/i>\n metabolite identification of brexpiprazole using ultra\u2010high\u2010performance liquid chromatography\/quadrupole time\u2010of\u2010flight mass spectrometry"],"prefix":"10.1002","volume":"33","author":[{"given":"Disha","family":"Thakkar","sequence":"first","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research\u2010Ahmedabad Palaj Gandhinagar Gujarat\u2010382355 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-488X","authenticated-orcid":false,"given":"Abhijeet S.","family":"Kate","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research\u2010Ahmedabad Palaj Gandhinagar Gujarat\u2010382355 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.04.012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3371\/CSRP.MCCI.010316"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0462-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0320-0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1086269"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574887112666170821114831"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2010.10.014"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.12.43"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinms.2017.11.001"},{"key":"e_1_2_6_11_1","unstructured":"Brexpiprazole: Pharmacology Review(s): Application Number: 205422Orig1s000 205422Orig2s000. Center for Drug Evaluation and Research Web site.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2015\/205422Orig1Orig2s000PharmR.pdf. Updated July 11 2014. Accessed March 20 2017."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu761"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci400518g"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.7982"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2018.05.008"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2015.10.023"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498258509045024"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Frcm.8436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.8436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rcm.8436","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.8436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T16:27:15Z","timestamp":1761496035000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.8436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,14]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,6,15]]}},"alternative-id":["10.1002\/rcm.8436"],"URL":"https:\/\/doi.org\/10.1002\/rcm.8436","archive":["Portico"],"relation":{},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"type":"print","value":"0951-4198"},{"type":"electronic","value":"1097-0231"}],"subject":[],"published":{"date-parts":[[2019,5,14]]},"assertion":[{"value":"2018-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}