{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:26:39Z","timestamp":1786692399119,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>For many years, it is known as Nitrosamines are responsible for carcinogenicity in human. These nitroso\u2010impurities were found detected in plastics, food items, cigarette, insect killer, water and alcoholic beverages. In 2018 EMA and USFDA claimed the presence of N\u2010nitrosodimethylamine in valsartan used for the treatment of hypertension. Consequently, to assess the adverse effects of nitrosamine generation during storage, in the course of production, or through contaminated supply chains, regulators have issued many guidelines. Hence, there is a crucial need for accurate evaluation technique to measure nitroso\u2010impurities in pharmaceutical products.<\/jats:p>\n                  <jats:p>According to the Carcinogenic Potency Categorization Approach, the allowable intake is 400\u2009ng\/day, which translates to an allowable limit of 16\u2009ppm for a 25\u2009mg daily dose. A study was then performed at 1.5\u2009ppm relative to sample concentration, which is less than 10% of this limit. The main aim of this development to optimize and prove suitability of a new liquid chromatography\u2013tandem mass spectrometry method for quantitatively analyzing 3\u2010amino\u2010N\u2010nitrosopiperidine (NTPA) in Alogliptin Benzoate (AGP), achieving detectable response of 0.03\u2009ppm and quantifiable response value of 0.1\u2009ppm relative to sample concentration. Current method was found to be linear with the coefficient of regression of 0.9979. Also, spiking study was performed by the calculating percentage spiked NTPA in the drug, which ranged from 96.67% to 100.14%. The results confirmed that the methodology was reliable, precise, robust and reproducible to quantify NTPA at 1.5\u2009ppm in samples of 2.75\u2009mg\/mL concentration.<\/jats:p>","DOI":"10.1002\/bmc.70578","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T08:27:02Z","timestamp":1785572822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trace Analysis of Genotoxic Impurity 3\u2010Amino\u2010N\u2010Nitrosopiperidine in Alogliptin Benzoate by Ultra\u2010Sensitive Liquid Chromatography Tandem Mass Spectrometry"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-1656","authenticated-orcid":false,"given":"Mithun M.","family":"Gharat","sequence":"first","affiliation":[{"name":"SIES College of Arts, Science and Commerce (Empowered Autonomous)  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0030-0448","authenticated-orcid":false,"given":"Pallavi T.","family":"Roy","sequence":"additional","affiliation":[{"name":"SIES College of Arts, Science and Commerce (Empowered Autonomous)  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit N.","family":"Gosar","sequence":"additional","affiliation":[{"name":"Analytical Research &amp; Development Department Indoco Remedies Limited  Navi Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-767X","authenticated-orcid":false,"given":"Tabrez A.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Analytical Research &amp; Development Department Indoco Remedies Limited  Navi Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-8109","authenticated-orcid":false,"given":"Suresh S.","family":"Shendage","sequence":"additional","affiliation":[{"name":"Department of Chemistry KET'S V. G. Vaze College of Arts, Science and Commerce (Autonomous)  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-0925","authenticated-orcid":false,"given":"Nitin A.","family":"Mirgane","sequence":"additional","affiliation":[{"name":"SIES College of Arts, Science and Commerce (Empowered Autonomous)  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573412917999201102212635"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2024.110828"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471463728"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-024-10000-w"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2024.11.003"},{"key":"e_1_2_11_7_1","unstructured":"EMA.2018. \u201cICH Q2(R2) Validation of Analytical Procedures \u2010 Scientific Guideline European Medicines Agency.\u201d European Medicines Agency.https:\/\/www.ema.europa.eu\/en\/ich\u2010q2r2\u2010validation\u2010analytical\u2010procedures\u2010scientific\u2010guideline."},{"key":"e_1_2_11_8_1","unstructured":"EMA.2019. \u201cupdate on Metformin Diabetes Medicines\u201d."},{"key":"e_1_2_11_9_1","unstructured":"EMA.2025. \u201cNitrosamine impurities in human medicines\u201d."},{"key":"e_1_2_11_10_1","unstructured":"European Medicines Agency.2023. \u201cICHM7 assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk \u2010 scientific guideline\u201d."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070104l"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70189"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70336"},{"issue":"7","key":"e_1_2_11_14_1","article-title":"Metabolism and Chemical Degradation of New Antidiabetic Drugs (Part II): A Review of Analytical Approaches for Analysis of Gliptins","volume":"11","author":"Gumieniczek A.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_11_15_1","unstructured":"Health Canada Government of Canada.2025. \u201cNitrosamine impurities in medications: Established acceptable intake limits\/AGP\u201d."},{"key":"e_1_2_11_16_1","unstructured":"ICH.2006. \u201cImpurities in new drug substances Q3A (R2)\u201d."},{"key":"e_1_2_11_17_1","unstructured":"ICH.2023. \u201cValidation of analytical procedures Q2 (R2).\u201dhttps:\/\/database.ich.org\/sites\/default\/files\/ICH_Q2(R2)_Guideline_2023_1130.pdf."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.04.032"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1956.15"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00234"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19370700410"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70150"},{"issue":"3","key":"e_1_2_11_23_1","first-page":"234","article-title":"A Validated Chiral HPLC Method for the Enantiomeric Purity of AGP","volume":"6","author":"Rao G. 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