{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:11:05Z","timestamp":1784113865923,"version":"3.55.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM122733"],"award-info":[{"award-number":["P30GM122733"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["2023\\u20131099"],"award-info":[{"award-number":["2023\\u20131099"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA050613"],"award-info":[{"award-number":["R01DA050613"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical and Biomedical Analysis"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.jpba.2026.117630","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T16:23:33Z","timestamp":1782318213000},"page":"117630","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Development and validation of a UPLC-MS\/MS method for real-time neuropharmacokinetic monitoring of iboga alkaloids in rat brain"],"prefix":"10.1016","volume":"280","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-8648","authenticated-orcid":false,"given":"Scot","family":"McIntosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4284-4177","authenticated-orcid":false,"given":"Isabella","family":"Maldonado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0850-8730","authenticated-orcid":false,"given":"Nickalus C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9425-3437","authenticated-orcid":false,"given":"Rama S.","family":"Gadepalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7355-6902","authenticated-orcid":false,"given":"John M.","family":"Rimoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6911-4669","authenticated-orcid":false,"given":"Vaclav","family":"Havel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalibor","family":"Sames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-1133","authenticated-orcid":false,"given":"Scott E.","family":"Hemby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpba.2026.117630_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106620","article-title":"IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy","volume":"190","author":"Mash","year":"2023","journal-title":"Pharmacol. Res."},{"issue":"3","key":"10.1016\/j.jpba.2026.117630_bib2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/105504999305848","article-title":"Treatment of acute opioid withdrawal with ibogaine","volume":"8","author":"Alper","year":"1999","journal-title":"Am. J. Addict."},{"key":"10.1016\/j.jpba.2026.117630_bib3","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1749-6632.2000.tb05213.x","article-title":"Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures","volume":"914","author":"Mash","year":"2000","journal-title":"Ann. N. Y Acad. Sci."},{"issue":"6","key":"10.1016\/j.jpba.2026.117630_bib4","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/cpdd.254","article-title":"Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients","volume":"5","author":"Glue","year":"2016","journal-title":"Clin. Pharmacol. Drug. Dev."},{"key":"10.1016\/j.jpba.2026.117630_bib5","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1749-6632.1998.tb08242.x","article-title":"Medication development of ibogaine as a pharmacotherapy for drug dependence","volume":"844","author":"Mash","year":"1998","journal-title":"Ann. N. Y Acad. Sci."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/jacs.5c06325","article-title":"Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses","volume":"148","author":"Hwu","year":"2026","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib7","doi-asserted-by":"crossref","first-page":"8118","DOI":"10.1038\/s41467-024-51856-y","article-title":"Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models","volume":"15","author":"Havel","year":"2024","journal-title":"Nat. Commun."},{"issue":"8","key":"10.1016\/j.jpba.2026.117630_bib8","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s11095-007-9502-2","article-title":"On the rate and extent of drug delivery to the brain","volume":"25","author":"Hammarlund-Udenaes","year":"2008","journal-title":"Pharm. Res."},{"issue":"4","key":"10.1016\/j.jpba.2026.117630_bib9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1124\/dmd.108.024125","article-title":"Unbound drug concentration in brain homogenate and cerebral spinal fluid at steady state as a surrogate for unbound concentration in brain interstitial fluid","volume":"37","author":"Liu","year":"2009","journal-title":"Drug. Metab. Dispos."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0165-0173(97)00014-3","article-title":"Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood-brain barrier","volume":"25","author":"de Lange","year":"1997","journal-title":"Brain Res. Brain Res. Rev."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib11","doi-asserted-by":"crossref","DOI":"10.1002\/cpph.38","article-title":"Quantitative intracerebral microdialysis studies to determine unbound extracellular fluid drug concentrations in discrete areas of the brain","volume":"80","author":"Durk","year":"2018","journal-title":"Curr. Protoc. Pharmacol."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2005.01.017","article-title":"Microdialysis--theoretical background and recent implementation in applied life-sciences","volume":"25","author":"Plock","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"issue":"3","key":"10.1016\/j.jpba.2026.117630_bib13","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0003-2670(98)00633-3","article-title":"A review of microdialysis sampling for pharmacokinetic applications","volume":"379","author":"Davies","year":"1999","journal-title":"Anal. Chim. Acta"},{"issue":"4","key":"10.1016\/j.jpba.2026.117630_bib14","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.talanta.2007.07.027","article-title":"Quantitative liquid chromatography\/mass spectrometry for the analysis of microdialysates","volume":"74","author":"Lanckmans","year":"2008","journal-title":"Talanta"},{"issue":"6","key":"10.1016\/j.jpba.2026.117630_bib15","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/jat\/19.6.427","article-title":"Identification and quantitation of ibogaine and an o-demethylated metabolite in brain and biological fluids using gas chromatography-mass spectrometry","volume":"19","author":"Hearn","year":"1995","journal-title":"J. Anal. Toxicol."},{"issue":"1-2","key":"10.1016\/j.jpba.2026.117630_bib16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jchromb.2005.06.018","article-title":"Quantitation of ibogaine and 12-hydroxyibogamine in human plasma by liquid chromatography with fluorimetric detection","volume":"822","author":"Kontrimaviciute","year":"2005","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"issue":"2","key":"10.1016\/j.jpba.2026.117630_bib17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jchromb.2006.05.035","article-title":"Liquid chromatography-electrospray mass spectrometry determination of ibogaine and noribogaine in human plasma and whole blood. Application to a poisoning involving Tabernanthe iboga root","volume":"843","author":"Kontrimaviciute","year":"2006","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.forsciint.2007.08.013","article-title":"Determination of ibogaine and noribogaine in biological fluids and hair by LC-MS\/MS after Tabernanthe iboga abuse Iboga alkaloids distribution in a drowning death case","volume":"176","author":"Cheze","year":"2008","journal-title":"Forensic Sci. Int."},{"issue":"20","key":"10.1016\/j.jpba.2026.117630_bib19","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S1359-6446(05)03620-2","article-title":"Principles and applications of LC-MS in new drug discovery","volume":"10","author":"Korfmacher","year":"2005","journal-title":"Drug. Discov. Today"},{"key":"10.1016\/j.jpba.2026.117630_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.aca.2022.340711","article-title":"From fundamentals in calibration to modern methodologies: A tutorial for small molecules quantification in liquid chromatography-mass spectrometry bioanalysis","volume":"1240","author":"Visconti","year":"2023","journal-title":"Anal. Chim. Acta"},{"issue":"13","key":"10.1016\/j.jpba.2026.117630_bib21","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1021\/ac020361s","article-title":"Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS\/MS","volume":"75","author":"Matuszewski","year":"2003","journal-title":"Anal. Chem."},{"key":"10.1016\/j.jpba.2026.117630_bib22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jpba.2018.03.052","article-title":"Quantitative evaluation of the matrix effect in bioanalytical methods based on LC-MS: A comparison of two approaches","volume":"155","author":"Rudzki","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"10.1016\/j.jpba.2026.117630_bib23","unstructured":"Food and Drug Administration. Bioanalytical Method Validation: Guidance for Industry. Center for Drug Evaluation and Research (CDER); Center for Veterinary Medicine (CVM). Washington, DC; 2018. \u3008https:\/\/www.fda.gov\/media\/70858\/download\u3009."},{"key":"10.1016\/j.jpba.2026.117630_bib24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jpba.2018.12.030","article-title":"Bioanalytical method validation: new FDA guidance vs. EMA guideline. Better or worse?","volume":"165","author":"Kaza","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"21","key":"10.1016\/j.jpba.2026.117630_bib25","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1021\/acs.orglett.7b02701","article-title":"B(C(6)F(5))(3)-Catalyzed Regioselective Deuteration of Electron-Rich Aromatic and Heteroaromatic Compounds","volume":"19","author":"Li","year":"2017","journal-title":"Org. Lett."},{"issue":"6","key":"10.1016\/j.jpba.2026.117630_bib26","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/1099-0801(200010)14:6<422::AID-BMC25>3.0.CO;2-I","article-title":"High-throughput quantitative bioanalysis by LC\/MS\/MS","volume":"14","author":"Jemal","year":"2000","journal-title":"Biomed. Chromatogr."},{"key":"10.1016\/j.jpba.2026.117630_bib27","series-title":"Liquid chromatography--mass spectrometry","author":"Niessen","year":"2006"},{"issue":"1","key":"10.1016\/j.jpba.2026.117630_bib28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0006-2952(94)00441-N","article-title":"S.D. Glick, Identification and quantification of the indole alkaloid ibogaine in biological samples by gas chromatography-mass spectrometry","volume":"49","author":"Gallagher","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.jpba.2026.117630_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.855000","article-title":"Drug transporters ABCB1 (P-gp) and OATP, but not drug-metabolizing enzyme CYP3A4, affect the pharmacokinetics of the psychoactive alkaloid ibogaine and its metabolites","volume":"13","author":"F. Martins","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"6","key":"10.1016\/j.jpba.2026.117630_bib30","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/jat\/19.6.381","article-title":"Determination of ibogaine and 12-hydroxy-ibogamine in plasma by gas chromatography-positive ion chemical ionization-mass spectrometry","volume":"19","author":"Alburges","year":"1995","journal-title":"J. Anal. Toxicol."},{"key":"10.1016\/j.jpba.2026.117630_bib31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jpba.2017.05.020","article-title":"Evaluation of pharmacokinetics and blood-brain barrier permeability of mitragynine using in vivo microdialysis technique","volume":"143","author":"Kong","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"1-2","key":"10.1016\/j.jpba.2026.117630_bib32","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/0006-8993(95)00123-8","article-title":"Radioligand-binding study of noribogaine, a likely metabolite of ibogaine","volume":"675","author":"Pearl","year":"1995","journal-title":"Brain Res."},{"key":"10.1016\/j.jpba.2026.117630_bib33","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.neuropharm.2015.08.032","article-title":"Noribogaine is a G-protein biased kappa-opioid receptor agonist","volume":"99","author":"Maillet","year":"2015","journal-title":"Neuropharmacology"},{"issue":"2","key":"10.1016\/j.jpba.2026.117630_bib34","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0022-3565(24)29567-7","article-title":"vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats","volume":"297","author":"Baumann","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"2","key":"10.1016\/j.jpba.2026.117630_bib35","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.jpba.2006.08.010","article-title":"Does a stable isotopically labeled internal standard always correct analyte response? A matrix effect study on a LC\/MS\/MS method for the determination of carvedilol enantiomers in human plasma","volume":"43","author":"Wang","year":"2007","journal-title":"J. Pharm. Biomed. Anal."}],"container-title":["Journal of Pharmaceutical and Biomedical Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0731708526002980?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0731708526002980?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:58:16Z","timestamp":1784113096000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0731708526002980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":35,"alternative-id":["S0731708526002980"],"URL":"https:\/\/doi.org\/10.1016\/j.jpba.2026.117630","relation":{},"ISSN":["0731-7085"],"issn-type":[{"value":"0731-7085","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Development and validation of a UPLC-MS\/MS method for real-time neuropharmacokinetic monitoring of iboga alkaloids in rat brain","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.2026.117630","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"117630"}}