{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:55:51Z","timestamp":1792706151216,"version":"4.5.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>N-nitrosamine impurities have been detected in a vast variety of drug substances and drug products, showing concern for regulatory aspects. To meet the regulatory requirement for the concerned impurity, a sensitive analytical method capable of quantifying these impurities at a lower level with accuracy and precision is required. This article focuses on the development and validation of an analytical method for the simultaneous detection of nine nitrosamine impurities in a single method for nebivolol drug product using liquid chromatography-mass spectrometry\/mass spectrometry-atmospheric pressure chemical ionization (LC-MS\/MS-APCI). The chromatographic separation was performed using the LC-MS column Allure BiPh C18 (250\u2009\u00d7 4.6\u00a0mm), 5\u00a0\u03bcm employed a gradient mode elution program using 0.002\u00a0M Ammonium acetate buffer pH\u00a04.5 as mobile phase A and methanol as mobile phase B. The method was challenged for accuracy, precision and linearity in accordance with International Council for Harmonization guidelines to ensure its suitability for the intended usage. The developed method was specific, accurate and linear with square of correlation coefficient (r2) found to be greater than 0.99 (0.9970\u20130.9992). The LOQ obtained in the range of 9.85\u201319.62\u00a0ppb for nine nitrosamines showed good sensitivity. The results demonstrated that method can be applied to quantify the nitrosamines in nebivolol drug products.<\/jats:p>","DOI":"10.1093\/chromsci\/bmae061","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T04:29:20Z","timestamp":1733977760000},"source":"Crossref","is-referenced-by-count":1,"title":["Chromatographic Separation and Quantification of Nine Nitrosamine Genotoxic Impurities in a Single Method in Nebivolol Tablet by Using Validated Ultra-Sensitive Liquid Chromatography: Mass Spectrometry Analytical Method"],"prefix":"10.1093","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8567-7481","authenticated-orcid":false,"given":"Mehul","family":"Pathak","sequence":"first","affiliation":[{"name":"Department of Chemistry, Smt. S.S. Patel Nootan Science & Commerce College, Sankalchand Patel University , Visnagar 384315 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-631X","authenticated-orcid":false,"given":"Dhara D","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Smt. S.S. Patel Nootan Science & Commerce College, Sankalchand Patel University , Visnagar 384315 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalip","family":"Kumar","sequence":"additional","affiliation":[{"name":"Analytical Research Laboratory, Cadila Pharmaceuticals Ltd., Dholka , Ahmedabad 382225 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avineesh","family":"Singh","sequence":"additional","affiliation":[{"name":"Analytical Research Laboratory, Cadila Pharmaceuticals Ltd., Dholka , Ahmedabad 382225 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Analytical Research Laboratory, Cadila Pharmaceuticals Ltd., Dholka , Ahmedabad 382225 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"2025010912420559100_ref1"},{"issue":"17","key":"2025010912420559100_ref2","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1056\/NEJMp1901657","article-title":"Hypertension hot potato \u2014 Anatomy of the angiotensin-receptor blocker recalls","volume":"380","author":"Byrd","year":"2019","journal-title":"New England Journal of Medicine."},{"key":"2025010912420559100_ref3","author":"ICH-M7 (R1); ICH Harmonized Guideline"},{"issue":"5","key":"2025010912420559100_ref4","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.3390\/ijms24054684","article-title":"DNA alkylation damage by nitrosamines and relevant DNA repair pathways","volume":"24","author":"Fahrer","year":"2023","journal-title":"International Journal of Molecular 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products","volume":"21","author":"Nasr","year":"2022","journal-title":"Expert Opinion on Drug Safety"},{"key":"2025010912420559100_ref8"},{"key":"2025010912420559100_ref9","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jpba.2018.11.010","article-title":"NDMA impurity in valsartan and other pharmaceutical products: Analytical methods for the determination of N-nitrosamines","volume":"164","author":"Parr","year":"2019","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"22","key":"2025010912420559100_ref10","doi-asserted-by":"crossref","first-page":"5304","DOI":"10.3390\/molecules25225304","article-title":"N-Nitrosodimethylamine contamination in the metformin finished products","volume":"25","author":"Zmys\u0142owski","year":"(2020","journal-title":"Molecules"},{"issue":"1","key":"2025010912420559100_ref11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.aca.2011.06.024","article-title":"Determination of eight nitrosamines in water at the ng L\u22121 levels by liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry","volume":"702","author":"Ripoll\u00e9s","year":"2011","journal-title":"Analytica Chimica Acta"},{"issue":"16","key":"2025010912420559100_ref12","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1016\/j.watres.2011.06.041","article-title":"Occurrence of nine nitrosamines and secondary amines in source water and drinking water: Potential of secondary amines as nitrosamine precursors","volume":"45","author":"Wang","year":"2011","journal-title":"Water Research"},{"issue":"10","key":"2025010912420559100_ref13","first-page":"1051","article-title":"Development and validation of a stability-indicating reverse phase ultra performance liquid chromatographic method for the estimation of nebivolol impurities in active pharmaceutical ingredients and pharmaceutical formulation","volume":"33","author":"Veera","year":"2015","journal-title":"Se Pu"},{"issue":"6","key":"2025010912420559100_ref14","first-page":"1","article-title":"Stability-indicating RP-UPLC method development and validation for the process related impurities of Nebivolol and structural characterization of its forced degradation products by LC-MS\/MS","volume":"14","author":"Kancherla","year":"2016","journal-title":"J Pharm Res Int."},{"issue":"6","key":"2025010912420559100_ref15","first-page":"411","article-title":"Development of validated stability-indicating chromatographic method for the determination of Nebivolol and valsartan and its related impurities in pharmaceutical tablets","volume":"14","author":"Gohel","year":"2023","journal-title":"Systematic Reviews in Pharmacy."}],"container-title":["Journal of Chromatographic 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