{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:51Z","timestamp":1790776731149,"version":"4.1.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.xphs.2026.104464","type":"journal-article","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T11:34:41Z","timestamp":1786880081000},"page":"104464","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eco-friendly stability-indicating HPLC method development, validation, and LC\u2013MS-based characterization of degradation products of the polar drug imeglimin"],"prefix":"10.1016","volume":"115","author":[{"given":"Vinod Rajaram","family":"Jejurkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-2840","authenticated-orcid":false,"given":"Charushila Jayant","family":"Bhangale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xphs.2026.104464_bib0001","unstructured":"International Conference on Harmonisation. Stability testing of new drug substances and products Q1A(R2). 2003. Available at: https:\/\/database.ich.org\/sites\/default\/files\/Q1A%28R2%29%20Guideline.pdf. Accessed January 12, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0002","series-title":"Pharmaceutical Stress Testing: Predicting Drug Degradation","author":"Baertschi","year":"2011"},{"issue":"6","key":"10.1016\/j.xphs.2026.104464_bib0003","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0731-7085(02)00047-X","article-title":"Development of validated stability-indicating assay methods\u2014critical review","volume":"28","author":"Bakshi","year":"2002","journal-title":"J Pharm Biomed Anal"},{"key":"10.1016\/j.xphs.2026.104464_bib0004","unstructured":"National Health Surveillance Agency. ANVISA Resolution No. 964. 2025. Available at: https:\/\/anvisalegis.datalegis.net\/action\/UrlPublicasAction.php?acao=abrirAtoPublico&num_ato=00000964&sgl_tipo=RDC&sgl_orgao=RDC\/DC\/ANVISA\/MS&vlr_ano=2025&seq_ato=000&cod_modulo=310&cod_menu=9434. Accessed October 15, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0005","unstructured":"European Medicines Agency. Nitrosamine impurities in human medicines. 2025. Available at: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/post-authorisation\/referral-procedures-human-medicines\/nitrosamine-impurities. Accessed October 15, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0006","unstructured":"Health Canada. Guidance on nitrosamine impurities in medications. 2025. Available at:https:\/\/www.canada.ca\/content\/dam\/hc-sc\/documents\/services\/drugs-health-products\/compliance-enforcement\/information-health-product\/drugs\/nitrosamine-impurities\/medications-guidance\/medications-guidance.pdf. Accessed October 15, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0007","unstructured":"Center for Drug Evaluation and Research. Control of nitrosamine impurities in human drugs guidance for industry. 2024. Available at: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/control-nitrosamine-impurities-human-drugs. Accessed October 15, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0008","unstructured":"Imeglimin. DrugBank. 2025. Available at: https:\/\/go.drugbank.com\/drugs\/DB12509. Accessed October 16, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0009","doi-asserted-by":"crossref","first-page":"9410","DOI":"10.1038\/s41598-024-60206-3","article-title":"Synthesis and molecular docking studies of new aryl imeglimin derivatives as a potent antidiabetic agent in a diabetic zebrafish model","volume":"14","author":"Khodakhah","year":"2024","journal-title":"Sci Rep"},{"issue":"12","key":"10.1016\/j.xphs.2026.104464_bib0010","doi-asserted-by":"crossref","first-page":"17842","DOI":"10.1021\/acsomega.8b02507","article-title":"Biguanide antidiabetic drugs: imeglimin exhibits higher proton basicity but smaller lithium-cation basicity than metformin in vacuo","volume":"3","author":"Raczy\u0144ska","year":"2018","journal-title":"ACS Omega"},{"issue":"4","key":"10.1016\/j.xphs.2026.104464_bib0011","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/ddr.21636","article-title":"A review of phenformin, metformin, and imeglimin","volume":"81","author":"Yendapally","year":"2020","journal-title":"Drug Dev Res"},{"issue":"6","key":"10.1016\/j.xphs.2026.104464_bib0012","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s13318-020-00642-4","article-title":"Lack of drug\u2013drug interaction between cimetidine, a renal transporter inhibitor, and imeglimin, a novel oral antidiabetic drug, in healthy volunteers","volume":"45","author":"Chevalier","year":"2020","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"10.1016\/j.xphs.2026.104464_bib0013","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s43094-025-00832-4","article-title":"Green bioanalytical method development and validation for estimation of Imeglimin hydrochloride using human plasma in pure form by LC\u2013MS\/MS","volume":"11","author":"Chandarana","year":"2025","journal-title":"Futur J Pharm Sci"},{"issue":"5","key":"10.1016\/j.xphs.2026.104464_bib0014","doi-asserted-by":"crossref","DOI":"10.1002\/rcm.9960","article-title":"Forced degradation study of an anti-diabetic drug imeglimin: impurity profiling and structure elucidation using LC-Q-ToF-MS\/MS and NMR","volume":"39","author":"Gogikar","year":"2025","journal-title":"Rapid Commun Mass Spectrom"},{"issue":"04","key":"10.1016\/j.xphs.2026.104464_bib0015","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.31788\/RJC.2024.1749002","article-title":"Forced degradation studies and assessment of degradation products of imeglimin hydrochloride using LC-ESI\/APCI-MS","volume":"17","author":"Talati","year":"2024","journal-title":"Rasayan J Chem"},{"key":"10.1016\/j.xphs.2026.104464_bib0016","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s41598-025-32999-4","article-title":"Stability indicating green HPLC method for imeglimin hydrochloride determination in pharmaceutical tablets with comprehensive assessment","volume":"16","author":"Mansour","year":"2026","journal-title":"Sci Rep"},{"issue":"6","key":"10.1016\/j.xphs.2026.104464_bib0017","doi-asserted-by":"crossref","first-page":"211","DOI":"10.22159\/ijap.2023v15i6.49757","article-title":"Development and validation of stability-indicating RP-UHPLC method for the estimation of imeglimin hydrochloride used for the treatment of metabolic disorder diabetes mellitus","volume":"15","author":"Jain","year":"2023","journal-title":"Int J Appl Pharm"},{"issue":"4","key":"10.1016\/j.xphs.2026.104464_bib0018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/CSJI\/2024\/v33i4901","article-title":"Stability indicating RP-HPLC method development and validation for imeglimin HCl in pharmaceutical dosage form","volume":"33","author":"Adhao","year":"2024","journal-title":"Chem Sci Int J"},{"issue":"2","key":"10.1016\/j.xphs.2026.104464_bib0019","doi-asserted-by":"crossref","first-page":"724","DOI":"10.25258\/ijddt.14.2.19","article-title":"Estimation of imeglimin in pharmaceutical tablets by RP-HPLC","volume":"14","author":"Jahagirdar","year":"2024","journal-title":"Int J Drug Deliv Technol"},{"issue":"4","key":"10.1016\/j.xphs.2026.104464_bib0020","first-page":"675","article-title":"Development and validation of RP-HPLC method for determination of antidiabetic drug (Imeglimin HCL) in bulk and its dosage form","volume":"14","author":"Chikhale","year":"2024","journal-title":"J Chem Health Risks"},{"issue":"4","key":"10.1016\/j.xphs.2026.104464_bib0021","doi-asserted-by":"crossref","first-page":"241","DOI":"10.22159\/ijap.2025v17i4.54506","article-title":"QbD (quality by design) approach: Development and validation of an RP-HPLC method for estimating imeglimin HCl and its ketone impurity","volume":"17","author":"Giri","year":"2025","journal-title":"Int J App Pharm"},{"issue":"7","key":"10.1016\/j.xphs.2026.104464_bib0022","doi-asserted-by":"crossref","first-page":"214","DOI":"10.7324\/JAPS.2023.132349","article-title":"A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio\u2014selective analysis of imeglimin in formulation","volume":"13","author":"Ramalingam","year":"2023","journal-title":"J Appl Pharm Sci"},{"issue":"12","key":"10.1016\/j.xphs.2026.104464_bib0023","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1016\/j.xphs.2023.09.003","article-title":"Pharmaceutical forced degradation (stress testing) endpoints: a scientific rationale and industry perspective","volume":"112","author":"Zelesky","year":"2023","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.xphs.2026.104464_bib0024","unstructured":"International Council for Harmonisation. Validation of analytical procedures Q2(R2). 2023. Avaialable at: https:\/\/database.ich.org\/sites\/default\/files\/ICH_Q2-R2_Document_Step2_Guideline_2022_0324.pdf. Accessed October 17, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0025","unstructured":"International Conference on Harmonisation, Stability testing: Photostability testing of new drug substances and products Q1B. 1996. Avaialable at: https:\/\/database.ich.org\/sites\/default\/files\/Q1B%20Guideline.pdf. Accessed October 18, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0026","unstructured":"International Agency for Research on Cancer. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: some pharmaceutical drugs. 1980. Available at: https:\/\/publications.iarc.who.int\/Book-And-Report-Series\/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans\/Some-Pharmaceutical-Drugs-1980. Accessed October 18, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0027","unstructured":"European Federation of Pharmaceutical Industries and Associations. Workflows for quality risk management of nitrosamine risks in medicines. 2022. Avaialable at: https:\/\/www.efpia.eu\/media\/676632\/efpia-nitrosamines-quality-risk-management-workflows-sep-2022.pdf. Accessed October 19, 2025."},{"issue":"2","key":"10.1016\/j.xphs.2026.104464_bib0028","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1590\/S1984-82502009000200007","article-title":"Robustness evaluation of the chromatographic method for the quantitation of lumefantrine using youden\u2019s test","volume":"45","author":"C\u00e9sar","year":"2009","journal-title":"Braz J Pharm Sci"},{"key":"10.1016\/j.xphs.2026.104464_bib0029","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.trac.2012.03.013","article-title":"Analytical Eco-Scale for assessing the greenness of analytical procedures","volume":"37","author":"Ga\u0142uszka","year":"2012","journal-title":"Trends Anal Chem"},{"issue":"14","key":"10.1016\/j.xphs.2026.104464_bib0030","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1021\/acs.analchem.0c01887","article-title":"AGREE\u2014Analytical GREEnness metric approach and software","volume":"92","author":"Pena-Pereira","year":"2020","journal-title":"Anal Chem"},{"key":"10.1016\/j.xphs.2026.104464_bib0031","series-title":"Liquid Chromatography","first-page":"343","article-title":"Solvent selection in liquid chromatography","author":"Ramis-Ramos","year":"2017"},{"key":"10.1016\/j.xphs.2026.104464_bib0032","series-title":"Relevant Applications of High-Performance Liquid Chromatography in Food, Environmental, Clinical and Biological Fields","article-title":"Optimizing ultra-high-performance liquid chromatography (UHPLC) methods for rapid analysis of complex biological samples","author":"Hymete","year":"2024"},{"issue":"1\u20132","key":"10.1016\/j.xphs.2026.104464_bib0033","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0021-9673(03)01216-0","article-title":"Slow equilibration of reversed-phase columns for the separation of ionized solutes","volume":"1015","author":"Marchand","year":"2003","journal-title":"J Chromatogr A"},{"issue":"34","key":"10.1016\/j.xphs.2026.104464_bib0034","doi-asserted-by":"crossref","first-page":"11692","DOI":"10.1021\/acs.analchem.1c01465","article-title":"CFM-ID 4.0: more accurate ESI-MS\/MS spectral prediction and compound identification","volume":"93","author":"Wang","year":"2021","journal-title":"Anal Chem"},{"key":"10.1016\/j.xphs.2026.104464_bib0035","series-title":"Pharmaceutical Stress Testing: Predicting Drug Degradation","first-page":"49","article-title":"Stress testing: the chemistry of drug degradation","author":"Baertschi","year":"2011"},{"key":"10.1016\/j.xphs.2026.104464_bib0036","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2020.113662","article-title":"Characterization of four major degradation products in metformin by 2D LC-QTOF\/MS\/MS","volume":"192","author":"Luo","year":"2021","journal-title":"J Pharm Biomed Anal"},{"key":"10.1016\/j.xphs.2026.104464_bib0037","unstructured":"Center for Drug Evaluation and Research. Reviewer guidance: validation of chromatographic methods. 1994. Available at: https:\/\/www.gmp-compliance.org\/files\/guidemgr\/1-6-13.pdf. Accessed March 18, 2025."},{"key":"10.1016\/j.xphs.2026.104464_bib0038","unstructured":"International Conference on Harmonisation. Impurities in new drug products Q3B(R2). 2006. Available at: https:\/\/database.ich.org\/sites\/default\/files\/Q3B%28R2%29%20Guideline.pdf. Accessed January 31, 2026."},{"key":"10.1016\/j.xphs.2026.104464_bib0039","unstructured":"International Conference on Harmonisation. Impurities in new drug substances Q3A(R2). 2006. Available at: https:\/\/database.ich.org\/sites\/default\/files\/Q3A%28R2%29%20Guideline.pdf. Accessed January 31, 2026."},{"key":"10.1016\/j.xphs.2026.104464_bib0040","series-title":"Pharmaceutical Stress Testing: Predicting Drug Degradation","first-page":"419","article-title":"Solid-state excipient compatibility testing","author":"Antipas","year":"2005"},{"key":"10.1016\/j.xphs.2026.104464_bib0041","series-title":"Pharmaceutical Stress Testing: Predicting Drug Degradation","first-page":"10","article-title":"Stress testing: a predictive tool","author":"Baertschi","year":"2011"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235492600314X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235492600314X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:24:06Z","timestamp":1790774646000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235492600314X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":41,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S002235492600314X"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2026.104464","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Eco-friendly stability-indicating HPLC method development, validation, and LC\u2013MS-based characterization of degradation products of the polar drug imeglimin","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2026.104464","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":"104464"}}