{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:38:09Z","timestamp":1767901089199,"version":"3.49.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical and Biomedical Analysis"],"published-print":{"date-parts":[[2023,10]]},"DOI":"10.1016\/j.jpba.2023.115626","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:32:24Z","timestamp":1690975944000},"page":"115626","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Benfluorex metabolism complemented by electrochemistry-mass spectrometry"],"prefix":"10.1016","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1454-4112","authenticated-orcid":false,"given":"Valentin","family":"G\u00f6ldner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Karst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpba.2023.115626_bib1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/ejechocard\/jeq172","article-title":"Valvular heart disease associated with benfluorex therapy: results from the French multicentre registry","volume":"12","author":"Le Ven","year":"2011","journal-title":"Eur. J. Echocardiogr."},{"key":"10.1016\/j.jpba.2023.115626_bib2","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/pds.3642","article-title":"Adverse effects of benfluorex on heart valves and pulmonary circulation","volume":"23","author":"Szymanski","year":"2014","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"10.1016\/j.jpba.2023.115626_bib3","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1002\/pds.2044","article-title":"Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus","volume":"19","author":"Weill","year":"2010","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"10.1016\/j.jpba.2023.115626_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0010128","article-title":"Benfluorex and unexplained valvular heart disease: a case-control study","volume":"5","author":"Frachon","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.jpba.2023.115626_bib5","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJM199608293350901","article-title":"Appetite-suppressant drugs and the risk of primary pulmonary hypertension","volume":"335","author":"Abenhaim","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jpba.2023.115626_bib6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM199708283370901","article-title":"Valvular heart disease associated with Fenfluramine\u2013Phentermine","volume":"337","author":"Connolly","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jpba.2023.115626_bib7","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1001\/jama.283.13.1703","article-title":"Valvular abnormalities and cardiovascular status following exposure to Dexfenfluramine or Phentermine\/Fenfluramine","volume":"283","author":"Gardin","year":"2000","journal-title":"JAMA"},{"key":"10.1016\/j.jpba.2023.115626_bib8","doi-asserted-by":"crossref","DOI":"10.1186\/1741-7015-6-34","article-title":"Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals","volume":"6","author":"Dahl","year":"2008","journal-title":"BMC Med"},{"key":"10.1016\/j.jpba.2023.115626_bib9","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1183\/09031936.00188611","article-title":"Pulmonary hypertension associated with benfluorex exposure","volume":"40","author":"Savale","year":"2012","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.jpba.2023.115626_bib10","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.3390\/children9081159","article-title":"Fenfluramine: a review of pharmacology, clinical efficacy, and safety in epilepsy","volume":"9","author":"Samanta","year":"2022","journal-title":"Children"},{"key":"10.1016\/j.jpba.2023.115626_bib11","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1161\/01.CIR.102.23.2836","article-title":"Evidence for possible involvement of 5-HT2B receptors in the cardiac valvulopathy associated with Fenfluramine and other serotonergic medications","volume":"102","author":"Rothman","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.jpba.2023.115626_bib12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0026-895X(24)26444-0","article-title":"Possible role of valvular serotonin 5-HT2B receptors in the cardiopathy associated with Fenfluramine","volume":"57","author":"Fitzgerald","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.jpba.2023.115626_bib13","first-page":"251","article-title":"Study on the excretion, localization and metabolism of a new anorexigenic substance: Fenfluramine","volume":"158","author":"Duhault","year":"1965","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"10.1016\/j.jpba.2023.115626_bib14","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/jps.2600570717","article-title":"Fenfluramine metabolism","volume":"57","author":"Bruce","year":"1968","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jpba.2023.115626_bib15","first-page":"465P","article-title":"Plasma concentrations of fenfluramine and its metabolite, norfenfluramine, after single and repeated oral administration","volume":"43","author":"Campbell","year":"1971","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jpba.2023.115626_bib16","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/j.2042-7158.1971.tb09899.x","article-title":"Determination of N-(2-benzoyloxyethyl)-norfenfluramine (JP 992) and its metabolites in urine","volume":"23","author":"Beckett","year":"1971","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jpba.2023.115626_bib17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.2042-7158.1972.tb08987.x","article-title":"The absorption, metabolism and elimination of (\u00b1)-N-(2-benzoyloxyethyl)norfenfluramine (JP992) in man","volume":"24","author":"Beckett","year":"1972","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jpba.2023.115626_bib18","first-page":"215","article-title":"Capmany, valvular heart disease associated with Benfluorex","volume":"56","author":"Rafel Ribera","year":"2003","journal-title":"Rev. Esp. Cardiol."},{"key":"10.1016\/j.jpba.2023.115626_bib19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1472-8206.2006.00441.x","article-title":"Valvular heart disease in a patient taking benfluorex","volume":"20","author":"Noize","year":"2006","journal-title":"Fundam. Clin. Pharmacol."},{"key":"10.1016\/j.jpba.2023.115626_bib20","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1183\/09031936.00086308","article-title":"Fenfluramine-like cardiovascular side-effects of benfluorex","volume":"33","author":"Boutet","year":"2009","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.jpba.2023.115626_bib21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.acvd.2009.09.015","article-title":"Valvular heart disease associated with benfluorex","volume":"103","author":"Gueffet","year":"2010","journal-title":"Arch. Cardiovasc. Dis."},{"key":"10.1016\/j.jpba.2023.115626_bib22","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1002\/rcm.978","article-title":"Comparison between electrochemistry\/mass spectrometry and cytochrome P450 catalyzed oxidation reactions","volume":"17","author":"Jurva","year":"2003","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"10.1016\/j.jpba.2023.115626_bib23","doi-asserted-by":"crossref","first-page":"12368","DOI":"10.1021\/ja052048o","article-title":"Model electrochemical-mass spectrometric studies of the cytochrome P450-catalyzed oxidations of cyclic tertiary allylamines","volume":"127","author":"Jurva","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.jpba.2023.115626_bib24","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1002\/rcm.3077","article-title":"Mimicry of phase I drug metabolism \u2013 novel methods for metabolite characterization and synthesis","volume":"21","author":"Johansson","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"10.1016\/j.jpba.2023.115626_bib25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.aca.2014.05.017","article-title":"Electrochemistry\/mass spectrometry as a tool in metabolism studies-a review","volume":"834","author":"Faber","year":"2014","journal-title":"Anal. Chim. Acta"},{"key":"10.1016\/j.jpba.2023.115626_bib26","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1021\/tx5001943","article-title":"Advances in the electrochemical simulation of oxidation reactions mediated by cytochrome P450","volume":"27","author":"Bussy","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.jpba.2023.115626_bib27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.trac.2015.02.017","article-title":"Electrochemistry-mass spectrometry to study reactive drug metabolites and CYP450 simulations","volume":"70","author":"Bussy","year":"2015","journal-title":"TrAC - Trends Anal. Chem."},{"key":"10.1016\/j.jpba.2023.115626_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/celc.202000442","article-title":"Recent developments in electrochemistry\u2013mass spectrometry","volume":"7","author":"Herl","year":"2020","journal-title":"ChemElectroChem"},{"key":"10.1016\/j.jpba.2023.115626_bib29","doi-asserted-by":"crossref","DOI":"10.1007\/s00216-023-04835-z","article-title":"Comparison of in vitro approaches for predicting the metabolism of the selective androgen receptor modulator RAD140","author":"Wagener","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.jpba.2023.115626_bib30","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1021\/acs.chemrestox.1c00288","article-title":"Electrochemical simulation of the oxidative capsaicin metabolism","volume":"34","author":"Kreidl","year":"2021","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.jpba.2023.115626_bib31","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00216-018-0933-x","article-title":"Prediction of biotransformation products of the fungicide fluopyram by electrochemistry coupled online to liquid chromatography-mass spectrometry and comparison with in vitro microsomal assays","volume":"410","author":"Mekonnen","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.jpba.2023.115626_bib32","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.jpha.2020.03.011","article-title":"Electrochemical and in silico approaches for liver metabolic oxidation of antitumor-active triazoloacridinone C-1305","volume":"10","author":"Pot\u0119ga","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"10.1016\/j.jpba.2023.115626_bib33","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41587-023-01690-2","article-title":"Integrative analysis of multimodal mass spectrometry data in MZmine 3","volume":"41","author":"Schmid","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jpba.2023.115626_bib34","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0009-2797(95)03624-U","article-title":"In vitro influence of benfluorex and its main metabolites on rat liver microsomal membrane properties","volume":"97","author":"Orsi\u00e8re","year":"1995","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.jpba.2023.115626_bib35","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00216-010-4455-4","article-title":"Screening for benfluorex and its major urinary metabolites in routine doping controls","volume":"401","author":"Thevis","year":"2011","journal-title":"Anal. Bioanal. Chem."}],"container-title":["Journal of Pharmaceutical and Biomedical Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0731708523003953?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0731708523003953?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T09:30:53Z","timestamp":1760002253000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708523003953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":35,"alternative-id":["S0731708523003953"],"URL":"https:\/\/doi.org\/10.1016\/j.jpba.2023.115626","relation":{},"ISSN":["0731-7085"],"issn-type":[{"value":"0731-7085","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Benfluorex metabolism complemented by electrochemistry-mass spectrometry","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical and Biomedical Analysis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpba.2023.115626","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115626"}}