{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:40:21Z","timestamp":1790444421165,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>2\u2010(2\u2010Chloroethoxy)ethanol (CEE) belongs to the so\u2010called cohort of concerns which were classified as highly potent mutagenic carcinogens by the World Health Organization. It is widely used in the synthesis of the essential anti\u2010histamine drug hydroxyzine. In addition, it is used as a primary solvent in dyes, nitrocellulose, paints, inks and resins. Owing to its potential genotoxicity, an efficient liquid chromatography\u2013tandem mass spectrometry method was developed for the quantitative estimation of CEE traces in an active pharmaceutical ingredients and in tablet dosage forms of hydroxyzine\u2010free base. The chromatographic separation was achieved on a C<jats:sub>18<\/jats:sub> column using a gradient elution mode with a binary solvent system (ammonium formate and methanol). Mass detection was performed for CEE using a positive mode with selected ion monitoring technique at <jats:italic>m\/z<\/jats:italic> value of [M\u2009+\u2009NH<jats:sub>4<\/jats:sub>]<jats:sup>+<\/jats:sup>. The developed method was validated as per the International Conference on Harmonizaiton guidelines. The quantitation limit, linearity and recoveries were found to be 0.56\u2009ppm, 0.56\u20137.49\u2009ppm (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u2009&gt;\u20090.9985) and 93.6\u201399.3%, respectively. The proposed method was highly compatible and was used effectively to estimate CEE traces in different stages of drug synthesis and in tablet dosage forms of hydroxyzine for routine and stability testing.<\/jats:p>","DOI":"10.1002\/bmc.5325","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T21:24:02Z","timestamp":1641504242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Development and validation of liquid chromatography\u2013tandem mass spectrometry method for the estimation of a potential genotoxic impurity 2\u2010(2\u2010chloroethoxy)ethanol in hydroxyzine"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2952-7493","authenticated-orcid":false,"given":"Narasimha S.","family":"Lakka","sequence":"first","affiliation":[{"name":"Division of Chemistry, Department of Sciences and Humanities VIGNAN\u2019s Foundation for Science, Technology &amp; Research  Vadlamudi Guntur (Dist.) India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3780-6222","authenticated-orcid":false,"given":"Chandrasekar","family":"Kuppan","sequence":"additional","affiliation":[{"name":"Division of Chemistry, Department of Sciences and Humanities VIGNAN\u2019s Foundation for Science, Technology &amp; Research  Vadlamudi Guntur (Dist.) India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima","family":"Ravinathan","sequence":"additional","affiliation":[{"name":"Department of Sciences and Humanities, JMJ College for Women  Tenali Guntur (Dist.) India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5658-8622","authenticated-orcid":false,"given":"Ashok Kumar","family":"Palakurthi","sequence":"additional","affiliation":[{"name":"Department of Analytical Research and Development Aurex Laboratories LLC  East Windsor NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"G3335","volume-title":"Familiarization guide. Agilent MassHunter workstation software data acquisition for 6200 series TOF and 6500 series Q\u2010TOF","author":"Agilent","year":"2007"},{"key":"e_1_2_8_3_1","first-page":"G3335","volume-title":"Familiarization guide. Agilent MassHunter workstation software quantitative analysis. Agilent Technologies, Inc. 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European Medicines Agency Evaluation of Medicines for Human Use.https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-limits-genotoxic-impurities_en.pdf"},{"key":"e_1_2_8_8_1","volume-title":"Safety working group, questions and answers on the \u2018Guideline on the limits of genotoxic impurities\u2019","author":"EMEA","year":"2010"},{"key":"e_1_2_8_9_1","first-page":"76361","volume-title":"FDA draft guidance, genotoxic and carcinogenic impurities in drug substances and products: Recommended approaches","author":"FDA","year":"2008"},{"key":"e_1_2_8_10_1","volume-title":"M7(R1): Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk, guidance for industry","author":"FDA","year":"2018"},{"key":"e_1_2_8_11_1","unstructured":"FDA. (2021). Hydroxyzine hydrochloride accessed on July 25 2021.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/088617Orig1s043 088618Orig1s043 088619Orig1s044lbl.pdf"},{"issue":"4","key":"e_1_2_8_12_1","first-page":"227","article-title":"Genotoxic impurities and its risk assessment in drug compounds","volume":"2","author":"Gosar A.","year":"2018","journal-title":"Drug Designing & Intellectual Properties International"},{"key":"e_1_2_8_13_1","unstructured":"ICH. (1996). Stability testing: Photostability testing of new drug substances and products Q1B current step 4 version dated 6 November 1996.https:\/\/database.ich.org\/sites\/default\/files\/Q1B%20Guideline.pdf"},{"key":"e_1_2_8_14_1","volume-title":"Stability testing of new drug substances and products Q1A (R2), current step 4 version, dated 6 February 2003","author":"ICH","year":"2003"},{"key":"e_1_2_8_15_1","volume-title":"Impurities: Guideline for residual solvents Q3C(R8), current step 4 version, dated 22 April 2021","author":"ICH","year":"2021"},{"key":"e_1_2_8_16_1","volume-title":"M7(R1) Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk","author":"ICH","year":"2021"},{"key":"e_1_2_8_17_1","unstructured":"ICH. (2005).Q2(R1) Validation of analytical procedures: Definitions and methodology. Incorporated in Q2(R1)"},{"key":"e_1_2_8_18_1","unstructured":"ICH. 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