{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:26:13Z","timestamp":1792517173788,"version":"4.5.0"},"reference-count":30,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100017499","name":"Dane O. Kildsig Center for Pharmaceutical Processing Research","doi-asserted-by":"publisher","award":["2025-01"],"award-info":[{"award-number":["2025-01"]}],"id":[{"id":"10.13039\/100017499","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.xphs.2026.104400","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:18:12Z","timestamp":1781885892000},"page":"104400","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recrystallization can stop nitrosamine formation in ranitidine hydrochloride"],"prefix":"10.1016","volume":"115","author":[{"given":"Jianchao","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1583-5767","authenticated-orcid":false,"given":"Yijing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4017-3259","authenticated-orcid":false,"given":"Jon","family":"Selbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4694-8353","authenticated-orcid":false,"given":"Lori","family":"Hilden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber S.","family":"Jannasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Huls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8154-6360","authenticated-orcid":false,"given":"Eric J.","family":"Munson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xphs.2026.104400_bib0001","series-title":"N-nitrosamines as Environmental Carcinogens","author":"Lijinsky","year":"1970"},{"issue":"5084","key":"10.1016\/j.xphs.2026.104400_bib0002","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/214169a0","article-title":"Evidence for the occurrence of N-nitrosamines in tobacco","volume":"214","author":"Serfontein","year":"1967","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.xphs.2026.104400_bib0003","first-page":"167","article-title":"Some toxic properties of dimethylnitrosamine","volume":"11","author":"Barnes","year":"1954","journal-title":"Br J Ind Med"},{"issue":"3","key":"10.1016\/j.xphs.2026.104400_bib0004","article-title":"Risk assessment of N-nitrosamines in food","volume":"21","author":"EPoCitF","year":"2023","journal-title":"Efsa J"},{"issue":"4","key":"10.1016\/j.xphs.2026.104400_bib0005","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/cts.12995","article-title":"Is this the end for ranitidine? NDMA presence continues to confound","volume":"14","author":"Wagner","year":"2021","journal-title":"Clin Transl Sci"},{"issue":"22","key":"10.1016\/j.xphs.2026.104400_bib0006","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1002\/ejoc.202100363","article-title":"The use of potassium\/sodium nitrite as a nitrosating agent in the electrooxidative n-nitrosation of secondary amines","volume":"2021","author":"Wang","year":"2021","journal-title":"Eur J Org Chem"},{"key":"10.1016\/j.xphs.2026.104400_bib0007","article-title":"Re: emery pharma citizen petition","volume":"2020","author":"RR","year":"2020","journal-title":"Emery Pharma"},{"issue":"9","key":"10.1016\/j.xphs.2026.104400_bib0008","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1248\/cpb.c21-00289","article-title":"N-Nitrosodimethylamine (NDMA) formation from ranitidine impurities: possible root causes of the presence of NDMA in ranitidine hydrochloride","volume":"69","author":"Yokoo","year":"2021","journal-title":"Chem Pharm Bull"},{"issue":"7","key":"10.1016\/j.xphs.2026.104400_bib0009","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1080\/14740338.2021.1917547","article-title":"Investigating the root cause of N-nitrosodimethylamine formation in metformin pharmaceutical products","volume":"20","author":"Nasr","year":"2021","journal-title":"Expert Opin Drug Saf"},{"key":"10.1016\/j.xphs.2026.104400_bib0010","series-title":"Laboratory tests\u2013Ranitidine","year":"2019"},{"key":"10.1016\/j.xphs.2026.104400_bib0011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-019-1376-1","article-title":"Lesson learnt from recall of valsartan and other angiotensin II receptor blocker drugs containing NDMA and NDEA impurities","volume":"20","author":"Charoo","year":"2019","journal-title":"AAPS PharmSciTech"},{"issue":"1","key":"10.1016\/j.xphs.2026.104400_bib0012","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-48344-5","article-title":"Rapid and efficient high-performance liquid chromatography analysis of N-nitrosodimethylamine impurity in valsartan drug substance and its products","volume":"9","author":"Masada","year":"2019","journal-title":"Sci Rep"},{"key":"10.1016\/j.xphs.2026.104400_bib0013","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jpba.2019.04.049","article-title":"Simultaneous detection of nitrosamines and other sartan-related impurities in active pharmaceutical ingredients by supercritical fluid chromatography","volume":"174","author":"Schmidtsdorff","year":"2019","journal-title":"J Pharm Biomed Anal"},{"issue":"2","key":"10.1016\/j.xphs.2026.104400_bib0014","first-page":"31","article-title":"Screening of nitrosamine impurities in sartan pharmaceuticals by GC-MS\/MS","volume":"12","author":"Chang","year":"2021","journal-title":"Mass Spectrom Lett"},{"issue":"12","key":"10.1016\/j.xphs.2026.104400_bib0015","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1021\/acs.oprd.0c00462","article-title":"Ranitidine\u2014investigations into the root cause for the presence of N-nitroso-N, N-dimethylamine in ranitidine hydrochloride drug substances and associated drug products","volume":"24","author":"King","year":"2020","journal-title":"Org Process Res Dev"},{"issue":"5","key":"10.1016\/j.xphs.2026.104400_bib0016","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.xphs.2022.11.011","article-title":"Ranitidine: a proposed mechanistic rationale for NDMA formation and a potential control strategy","volume":"112","author":"Harmon","year":"2023","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.xphs.2026.104400_bib0017","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2024.124832","article-title":"Nitrosamine mitigation: NDMA impurity formation and its inhibition in metformin hydrochloride tablets","volume":"666","author":"Shakleya","year":"2024","journal-title":"Int J Pharm"},{"key":"10.1016\/j.xphs.2026.104400_bib0018","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.xphs.2025.01.016","article-title":"Risk assessment and management strategy of two new nitrosamine drug substance related impurities (NDSRIs) in a pharmaceutical drug product for the treatment of a rare disease- From prediction to control","volume":"114","author":"Mukherjee","year":"2025","journal-title":"J Pharm Sci"},{"issue":"3","key":"10.1016\/j.xphs.2026.104400_bib0019","doi-asserted-by":"crossref","first-page":"893","DOI":"10.13005\/bbra\/3272","article-title":"Nitrosamine contamination in pharmaceuticals: a comprehensive review on nitrosation pathways, potential root cause, detection, risk assessment, and mitigation strategies","volume":"21","author":"Ukhade","year":"2024","journal-title":"Biosci Biotechnol Res Asia"},{"issue":"7","key":"10.1016\/j.xphs.2026.104400_bib0020","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.xphs.2023.03.022","article-title":"N-nitrosamine mitigation with nitrite scavengers in oral pharmaceutical drug products","volume":"112","author":"Bayne","year":"2023","journal-title":"J Pharm Sci"},{"issue":"8","key":"10.1016\/j.xphs.2026.104400_bib0021","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.3390\/pharmaceutics15082015","article-title":"Modeling the impact of excipients selection on nitrosamine formation towards risk mitigation","volume":"15","author":"Berardi","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.xphs.2026.104400_bib0022","unstructured":"Berardi A., Janssen P.H., Dickhoff B.H., van Gessel S., Pharma D. Nitrosamines risk mitigation."},{"issue":"2","key":"10.1016\/j.xphs.2026.104400_bib0023","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1208\/s12249-023-02523-w","article-title":"Nitroso impurities in drug products: an overview of risk assessment, regulatory milieu, and control strategy","volume":"24","author":"Charoo","year":"2023","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.xphs.2026.104400_bib0024","series-title":"FDA Approves Reformulated Ranitidine Following Comprehensive Safety Review | FDA. New Formulation Addresses Previous NDMA Impurity Formation Concerns","author":"FDA","year":"2025"},{"key":"10.1016\/j.xphs.2026.104400_bib0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.xphs.2025.103960","article-title":"Crystal defect causes nitrosamine formation in ranitidine under accelerate storage condition","volume":"114","author":"Xu","year":"2025","journal-title":"J Pharm Sci"},{"issue":"8","key":"10.1016\/j.xphs.2026.104400_bib0026","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1205\/cherd.05148","article-title":"Laboratory scale batch crystallization and the role of vessel size","volume":"84","author":"Yi","year":"2006","journal-title":"Chem Eng Res Des"},{"key":"10.1016\/j.xphs.2026.104400_bib0027","doi-asserted-by":"crossref","unstructured":"Yu Z.-Q., Yeoh A., Chow P.S., Tan R.B.H. 2016. Particle size control in batch crystallization of pyrazinamide on different scales. Organic Process Res Dev 20(12):2100\u20132107.","DOI":"10.1021\/acs.oprd.6b00327"},{"key":"10.1016\/j.xphs.2026.104400_bib0028","unstructured":"FDA US. 2019. Liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) method for the determination of NDMA in ranitidine drug substance and solid dosage drug product. ed."},{"key":"10.1016\/j.xphs.2026.104400_bib0029","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1208\/s12249-012-9879-z","article-title":"Investigating gabapentin polymorphism using solid-state NMR spectroscopy","volume":"14","author":"Dempah","year":"2013","journal-title":"AAPS Pharmscitech"},{"issue":"10","key":"10.1016\/j.xphs.2026.104400_bib0030","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1248\/cpb.c20-00431","article-title":"Temperature-dependent formation of N-nitrosodimethylamine during the storage of ranitidine reagent powders and tablets","volume":"68","author":"Abe","year":"2020","journal-title":"Chem Pharm Bull"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354926002492?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354926002492?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:33:20Z","timestamp":1788507200000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022354926002492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S0022354926002492"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2026.104400","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Recrystallization can stop nitrosamine formation in ranitidine hydrochloride","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2026.104400","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Pharmacists Association\u00ae. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104400"}}