{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:53:02Z","timestamp":1792291982473,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The present study aims to establish structures of the degradation products of an anti\u2010diabetic drug, Imeglimin (IMG) approved for the treatment of type 2 diabetes mellitus in the year 2021. Degradation pathways are proposed along with in silico toxicity assessments of the observed degradation products (DPs) of the drug.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A reversed\u2010phase high\u2010performance liquid chromatography (RP\u2010HPLC), equipped with a photodiode array detector, was used to separate the observed DPs with a Phenomenex Luna PFP (250\u2009\u00d7\u20094.6\u2009mm, 5\u2009\u03bcm) column, using 10\u2009mM ammonium formate (pH\u20094.5) and methanol as mobile phase. Liquid chromatography quadrupole time of flight mass spectrometry (LC\u2010Q\u2010ToF\u2010MS\/MS) and nuclear magnetic resonance (NMR) spectroscopy were employed for structural elucidation. Zeneth and Derek suites were used for in silico assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of four degradation products were observed, which were successfully separated on an RP\u2010HPLC. The structural characterization of three of the four DPs was achieved using LC\u2010Q\u2010TOF\u2010MS\/MS by employing electro spray ionization as well as atmospheric pressure chemical ionization. Additionally, DP\u20103 was isolated using a preparative HPLC and was characterized by NMR. Computationally predicted structures were compared with the experimental observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An HPLC method, capable of separating the Imeglimin and its four DPs, was developed and validated as per the ICH Q2(R1) guideline. Structure elucidation reveals a variety of products with metformin as one of the identified DPs along with a metabolite. The toxicity potential of DPs was assessed through docking studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.9960","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T23:39:19Z","timestamp":1733873959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Forced Degradation Study of an Anti\u2010Diabetic Drug Imeglimin: Impurity Profiling and Structure Elucidation Using LC\u2010Q\u2010ToF\u2010MS\/MS and NMR"],"prefix":"10.1002","volume":"39","author":[{"given":"Shiva\u00a0Kumar","family":"Gogikar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-9294","authenticated-orcid":false,"given":"Sibu","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivashankar","family":"Pathinti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gananadhamu","family":"Samanthula","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol\u00a0G.","family":"Dikundwar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-015-0099-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0763"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01611.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21636"},{"key":"e_1_2_10_6_1","unstructured":"B.ListandX.Cheng \u201cProcess for Preparing 3 6\u2010Dihydro\u20101 3 5\u2010triazine Derivatives.\u201d U. 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U.S. Patent and Trademark Office."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2014.38.4.261"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00253736"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90129-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14277"},{"key":"e_1_2_10_11_1","unstructured":"Imeglimin Hydrochloride accessed 4 June 2024 https:\/\/go.drugbank.com\/drugs\/DB12509."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000154"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00948-1"},{"issue":"7","key":"e_1_2_10_14_1","first-page":"214","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 S.","year":"2023","journal-title":"Journal of Applied Pharmaceutical Science"},{"issue":"5","key":"e_1_2_10_15_1","first-page":"366","article-title":"Development and Validation of RP\u2010HPLC Method for Estimation of Anti\u2010Diabetic Drug in Bulk and Tablet Dosage Form","volume":"10","author":"Salvi A. S.","year":"2023","journal-title":"Journal of Emerging Technologies and Innovative Research (JETIR)."},{"issue":"12","key":"e_1_2_10_16_1","first-page":"1","article-title":"A Novel Method Development and Validation of Imeglimin HCl by UV Visible Spectroscopy","volume":"1","author":"Tamil Selvan R.","year":"2023","journal-title":"International Journal of Pharmaceutical Sciences"},{"issue":"6","key":"e_1_2_10_17_1","first-page":"211","article-title":"Development and Validation of Stability Indicating RP\u2010UHPLC Method for the Estimation of Imeglimin Hydrochloride Used for the Treatment of Metabolic Disorder Diabetes Mellitus","volume":"15","author":"Jain A. S. L. 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