{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:26:44Z","timestamp":1786692404206,"version":"build-2736575974"},"reference-count":32,"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>Benzene (BENZ) is classified as a Class 1 residual solvent according to ICH Q3C guidelines due to its established classification as a Group 1 human carcinogen. During the chemical production of Cetirizine Dihydrochloride (CTZ) API, Cetirizine Dihydrochloride tablet (CTZT), Levocetirizine Dihydrochloride (LCTZ) API, and Levocetirizine Dihydrochloride tablet (LCTZT), BENZ can appear as a residual process impurity with carcinogenic risk; development of a highly sensitive quantification method is a critical requirement for pharmaceutical quality control. This study focused on developing and validating a method for detecting trace\u2010level BENZ in CTZ and LCTZ drug substance and drug product. The method demonstrated exceptional sensitivity, with a least detectable concentration of 0.04\u2009ppm and a quantifiable concentration of 0.12\u2009ppm, significantly lower than the ICH\u2010mandated safety limit of 2\u2009ppm. Linearity and accuracy studies yielded an outstanding percentage of samples spiked BEN in the drug substance and drug product of CTZ and LCTZ and found within acceptance limit, approving the method's validity in presence of the drug atmosphere. Conventional headspace GC\u2010FID\/GC\u2010MS are established techniques for benzene analysis; the proposed HPLC method offers a simpler, cost\u2010effective, and validated method, making it well suited for routine quality control laboratories where GC facilities may not be readily available.<\/jats:p>","DOI":"10.1002\/bmc.70584","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T08:05:33Z","timestamp":1785571533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultra\u2010Sensitive and Validated method for Trace Quantification of Carcinogenic Benzene in Cetirizine Dihydrochloride"],"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  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  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\/0000-0001-5413-0925","authenticated-orcid":false,"given":"Nitin A.","family":"Mirgane","sequence":"additional","affiliation":[{"name":"SIES College of Arts, Science and Commerce  Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"American Cancer Society.2023. \u201cBENZ and Cancer Risk.\u201dhttps:\/\/www.cancer.org\/cancer\/risk\u2010prevention\/chemicals\/BENZ.html."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201700685"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jfca.1995.1018"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199040050-00009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464050-00008"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202204041"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70189"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70336"},{"key":"e_1_2_8_10_1","unstructured":"International Agency for Research on Cancer.2018. \u201cIARC Monographs on the Identification of Carcinogenic Hazards to Humans Volume 120.\u201dhttps:\/\/publications.iarc.who.int\/Book\u2010And\u2010Report\u2010Series\/Iarc\u2010Monographs\u2010On\u2010The\u2010Identification\u2010Of\u2010Carcinogenic\u2010Hazards\u2010To\u2010Humans\/BENZ\u20102018."},{"key":"e_1_2_8_11_1","unstructured":"International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use.2021. \u201cImpurities: Guideline for Residual Solvents Q3C(R8).\u201dhttps:\/\/database.ich.org\/sites\/default\/files\/ICH_Q3CR8_Guideline_Step4_2021_0422_1.pdf."},{"key":"e_1_2_8_12_1","unstructured":"International Council for Harmonisation of Technical Requirement for Pharmaceuticals for Human Use.2023. \u201cICH Harmonised Guideline. Validation of Analytical Procedures Q2 (R2).\u201d"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202504531"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201600237"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5575"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/605381"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jics.2023.101060"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/812701"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201601174"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5336"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202200147"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talo.2023.100221"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5755"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.greeac.2024.100188"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70150"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2670(03)00339-8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826076.2011.585485"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-2361(02)00157-6"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2025.105970"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.22159\/ijap.2019v11i1.28983"},{"key":"e_1_2_8_31_1","unstructured":"U.S. Food and Drug Administration.2024. \u201cValidation of Analytical Procedures Q2 (R2).\u201dhttps:\/\/www.fda.gov\/media\/161201\/download."},{"key":"e_1_2_8_32_1","unstructured":"U.S. Food and Drug Administration.2025. \u201cFDA Alerts Drug Manufactures to the Risk of BENZ Contamination in Certain Drugs.\u201dhttps:\/\/www.fda.gov\/drugs\/pharmaceutical\u2010quality\u2010resources\/fda\u2010alerts\u2010drug\u2010manufacturers\u2010risk\u2010BENZ\u2010contamination\u2010certain\u2010drugs."},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202405405"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70584","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.70584","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:31:08Z","timestamp":1786689068000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/bmc.70584"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70584","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]},"assertion":[{"value":"2026-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70584"}}