{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T12:54:53Z","timestamp":1764420893558,"version":"3.46.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A robust and sensitive reversed\u2010phase HPLC method was developed and validated for the quantitative determination of 3\u2010methyl benzyl chloride, a potential genotoxic process impurity, in Meclizine HCl formulations. The separation was achieved on a C18 column using an isocratic mobile phase consisting of a 0.025\u2010M sodium 1\u2010heptanesulfonate buffer (pH\u20094.0, adjusted with 0.1\u2009N sulfuric acid) and acetonitrile (600:400, v\/v). Detection was performed at 210\u2009nm. A quality\u2010by\u2010design approach, specifically a Box\u2013Behnken design, was employed to optimize key chromatographic parameters including flow rate, acetonitrile concentration, and column temperature. The impact of these critical method variables was evaluated on retention time, tailing factor, and theoretical plate count to ensure method robustness and optimal performance. The method was validated per ICH guidelines, assessing specificity, linearity, accuracy, precision, robustness, and limits of detection (LOD) and quantification (LOQ). The LOD and LOQ were determined to be 0.016% and 0.048%, respectively, allowing for trace\u2010level detection of 3\u2010methyl benzyl chloride. The method demonstrated excellent specificity, sensitivity, accuracy (recoveries 95.1%\u2013102.1%), and precision (RSD\u2009\u2264\u200910.0%). This validated and QbD\u2010optimized method is suitable for routine quality control analysis in pharmaceutical manufacturing, ensuring the safety and regulatory compliance of Meclizine HCl formulations.<\/jats:p>","DOI":"10.1002\/bmc.70238","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:35:02Z","timestamp":1761204902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["QbD\u2010Based HPLC Method Development for Trace\u2010Level Detection of Genotoxic 3\u2010Methylbenzyl Chloride in Meclizine HCl Formulations"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4007-8797","authenticated-orcid":false,"given":"Naga\u00a0Kranthi\u00a0Kumar","family":"Chintalapudi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences Vignan's Foundation for Science, Technology and Research  Guntur Andhra Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naresh","family":"Podila","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences Vignan's Foundation for Science, Technology and Research  Guntur Andhra Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-5244","authenticated-orcid":false,"given":"Vijay\u00a0Kumar","family":"Chollety","sequence":"additional","affiliation":[{"name":"Ascent Pharmaceuticals Inc  Central Islip New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Drug Future.2023.Meclizine Hydrochloride USP Monograph. Retrieved from the Drug Future database."},{"key":"e_1_2_8_3_1","unstructured":"Drugs.com.2023.Meclizine Hydrochloride\u2014Uses Side Effects and More. Retrieved fromhttps:\/\/www.drugs.com."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.6001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70129"},{"key":"e_1_2_8_6_1","unstructured":"ICH.2005.Validation of Analytical procedures: Text and methodology Q2 (R1) current step 4 version dated 1996 and 2005.https:\/\/database.ich.org\/sites\/default\/files\/Q2%28R1%29%20Guideline.pdf."},{"volume-title":"Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk (M7 (R1))","year":"2017","author":"ICH","key":"e_1_2_8_7_1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5062"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.70007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.18520\/cs\/v114\/i03\/644-649"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/22297928.2019.1673814"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2003.08.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5687"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11094-024-03279-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5486"},{"volume-title":"Martindale: The Complete Drug Reference (41sted.)","year":"2022","author":"Sweetman S. 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Retrieved fromhttps:\/\/www.drugfuture.com\/Pharmacopoeia\/USP32."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5585"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T12:52:26Z","timestamp":1764420746000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/bmc.70238"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70238","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"type":"print","value":"0269-3879"},{"type":"electronic","value":"1099-0801"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"2025-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70238"}}