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Apixaban is subjected to stringent testing for potential genotoxic impurities during its manufacturing, due to its structure indicating the possibility of such impurity's formation. Setting limits in accordance with ICH M7 guidelines is essential to reduce patient exposure and also recommended an advanced analytical tool for testing. The present study aims to establish limits based on computational toxicological evaluation, and develop and validate a highly sensitive LS\u2010MS\/MS method for quantifying three novel genotoxic impurities of apixaban, namely impurities F, G, and H. The method was established utilizing a mobile phase comprising a pH\u20095.5 acetate buffer and acetonitrile in a gradient mode. Used a C18 column, of 150\u2009mm (length) \u00d7 3.0\u2009mm (width), 2.7\u2009\u03bcm of particle size as stationary phase. Quantification was performed with multi\u2010response monitoring in mass spectrometry, employing precursor ions of m\/z 437.2, 525.2, and 569.1 for impurities F, G, and H, respectively. The established method is validated for its intended use in accordance with regulatory guidelines and found suitable.<\/jats:p>","DOI":"10.1002\/bmc.70043","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:41:22Z","timestamp":1741732882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel Genotoxic Impurities in the First\u2010Line Oral Anticoagulant Drug, Apixaban: Computational Toxicological Evaluation and Development of a Highly Sensitive LC\u2010MS\/MS Quantification Method"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6412-8182","authenticated-orcid":false,"given":"Bhaskar","family":"Vallamkonda","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Science, School of Applied Sciences and Humanities Vignan's Foundation for Science, Technology &amp; Research  Guntur Andhra Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-9668","authenticated-orcid":false,"given":"Srinivasa\u00a0Rao","family":"Yarguntla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis Vignan Institute of Pharmaceutical Technology  Visakhapatnam Andhra Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8855-1047","authenticated-orcid":false,"given":"Ranadheer\u00a0Reddy","family":"Challa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, School of Applied Sciences and Humanities Vignan's Foundation for Science, Technology &amp; Research  Guntur Andhra Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"\u27e81225\u27e9 Validation of Compendial Procedures.2021.United States Pharmacopeia.https:\/\/doi.org\/10.31003\/uspnf_m99945_04_01.","DOI":"10.31003\/USPNF_M99945_04_01"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1207541"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1302507"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945012800564059"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5805"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2016.02.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5316"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809349195"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000775\u2010z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1007432"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2024.2367561"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00706\u2010023\u201003143\u20107"},{"key":"e_1_2_9_14_1","volume-title":"Guidelines on the Limit of Genotoxic Impurities","author":"EMEA","year":"2006"},{"key":"e_1_2_9_15_1","volume-title":"Guidance for Industry: Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches","author":"FDA","year":"2008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22077"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.6027"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2006.05.011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2007.10.038"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1107039"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2014.03.032"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm173"},{"key":"e_1_2_9_23_1","unstructured":"ICH.2022.Harmonized Tripartite Guideline. 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