{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:13:27Z","timestamp":1787235207706,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"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":[[2026,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Genotoxic impurities (GTIs) in pharmaceutical products represent a critical safety concern because they can induce DNA damage and may lead to mutagenic and carcinogenic effects even at trace concentrations. Consequently, regulatory authorities such as EMA, FDA, and ICH require a risk\u2010based and impurity\u2010specific control strategy, as defined in ICH M7, for active pharmaceutical ingredients (APIs) and finished dosage forms. Due to their structural and physicochemical diversity, GTIs cannot be adequately monitored using a single analytical technique, and method selection must be tailored to the characteristics of each impurity. In this study, impurity\u2010specific analytical methods were developed and validated to demonstrate the practical application of this regulatory approach in different pharmaceutical matrices. GC\u2013MS method was optimized for the determination of volatile alkylating agents, namely methyl, ethyl, and isopropyl methanesulfonate in imatinib mesylate API. LC\u2013MS\/MS method was established for the quantification of 5\u2010(4\u2032\u2010(azidomethyl)\u2010[1,1\u2032\u2010biphenyl]\u20102\u2010yl)\u20101H\u2010tetrazole, a polar and thermolabile azido impurity in valsartan formulations. Both methods were validated in accordance with ICH Q2(R1) guidelines, demonstrating excellent specificity, linearity (\n R<\/jats:italic>\n 2<\/jats:sup>\n \u2009>\u20090.999), accuracy, and precision, with detection limits sufficient to meet regulatory requirements. Application to commercial products confirmed the robustness of methods and their suitability for routine quality control supporting effective GTI risk management.\n <\/jats:p>","DOI":"10.1002\/bmc.70357","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:43:45Z","timestamp":1768805025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validated GC\u2013MS and LC\u2013MS\/MS Methods for ICH M7\u2013Based Quantification of Alkyl Mesylate and Azido Genotoxic Impurities in Pharmaceutical Products"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-8440","authenticated-orcid":false,"given":"Ne\u015fet","family":"Ne\u015feto\u011flu","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy Istanbul University Istanbul Turkey"},{"name":"Drug Application and Research Center Istanbul University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-1240","authenticated-orcid":false,"given":"Duri\u015fehvar\u00a0\u00d6zer","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy Istanbul University Istanbul Turkey"},{"name":"Drug Application and Research Center Istanbul University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809349195"},{"key":"e_1_2_8_3_1","unstructured":"European Medicines Agency (EMEA).2006a.ICH Topic Q 3 A (R2) Impurities in New Drug Substances."},{"key":"e_1_2_8_4_1","unstructured":"European Medicines Agency (EMEA).2006b.ICH Topic Q 3 B (R2) Impurities in New Drug Products."},{"key":"e_1_2_8_5_1","unstructured":"European Medicines Agency (EMEA).2010. \u201cGuideline on the Limits of Genotoxic Impurities Questions and Answers on the Guideline on the Limits of Genotoxic Impurities.\u201d 23 September 2010."},{"key":"e_1_2_8_6_1","unstructured":"Food and Drug Administration (FDA).2008. \u201cGenotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches.\u201d Washington DC USA."},{"key":"e_1_2_8_7_1","unstructured":"International Conference on Harmonisation (ICH).2015.Guideline Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7 (R1)."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.114300"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4137\/aci.s6471"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2004.06.095"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/chem\u20102020\u20100093"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2007.11.013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.20883\/medical.e502"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/0250\u2010474X.89769"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300095f"},{"key":"e_1_2_8_16_1","first-page":"11","article-title":"Determination of Methyl Methanesulfonate, Ethyl Methanesulfonate and Isopropyl Methanesulfonate Impurities in Lopinavir API by GC\/MS\/MS Using Electron Ionization","volume":"3","author":"Veenaeesh P.","year":"2014","journal-title":"International Journal of Pharma Research & Review"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27134129"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2023.104951"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2011.11.008"}],"container-title":["Biomedical 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