{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:46:16Z","timestamp":1774442776791,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"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":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Potential genotoxic impurities (PGI) and <jats:italic>N<\/jats:italic>\u2010nitrosamine impurities in active pharmaceutical ingredients (APIs) and their determination at low levels are substantial challenges for cholesterol\u2010lowering agents in recent years. Herein we developed a robust, reliable, rapid, accurate and validated technique of gas chromatography equipped with a mass spectrometer (GC\u2013MS) for quantifying subtle levels of 1,3\u2010dichloro\u20102\u2010propanol (PGI\u2010I) and 2,3\u2010dichloro\u20101\u2010propanol (PGI\u2010II) in colesevelam hydrochloride drug substance (bile acid sequestrant). The separation of colesevelam hydrochloride, PGI\u2010I and PGI\u2010II was executed with chromatographic technique using a capillary column, DB\u2010624 measuring with 30\u2009m\u2009\u00d7\u20090.32\u2009mm\u2009\u00d7\u20091.8\u00a0\u03bcm specification of 6% cyanopropylphenyl\u201094% dimethylpolysiloxane copolymer and helium carrier gas. This developed technique gave a good intensity peak without any interference and extra masses at the retention times of 11.17\u2009min for PGI\u2010I and 11.59\u2009min for PGI\u2010II, which was adequate, with mass spectra (<jats:italic>m<\/jats:italic>\/<jats:italic>z<\/jats:italic>) of 79 and 62, respectively. The method\u2019s sensitivity and linearity are demonstrated by its detection and quantification limits at subtle levels with correlation coefficients of 0.9965 for PGI\u2010I and 0.9910 for PGI\u2010II. The determination is mainly focused on improving sensitivity with the limits of detection and quantitation far below the specifications, which can support tighter limits. This results in a cost\u2010effective and easily adoptable methodology having precise and accurate results in colesevelam hydrochloride API\u00a0at subtle levels.<\/jats:p>","DOI":"10.1002\/bmc.5528","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T10:01:37Z","timestamp":1666000897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification and validation of potential genotoxic impurities, 1,3\u2010dichloro\u20102\u2010propanol, and 2,3\u2010dichloro\u20101\u2010propanol, at subtle levels in a bile acid sequestrant, colesevelam hydrochloride, using hyphenated GC\u2013MS technique"],"prefix":"10.1002","volume":"37","author":[{"given":"S. R. Jythesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Chemistry GITAM School of Science  Hyderabad Telangana India"},{"name":"Department of Analytical Research Aurobindo Pharma Limited Research Center\u2010II, Indrakarn (V), Kandi (M)  Sangareddy Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junuthula Venkata Ramana","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Analytical Research Aurobindo Pharma Limited Research Center\u2010II, Indrakarn (V), Kandi (M)  Sangareddy Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-4571","authenticated-orcid":false,"given":"Vandavasi Koteswara","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Chemistry GITAM School of Science  Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmw070"},{"key":"e_1_2_6_3_1","unstructured":"Deductive Estimation of Risk from Existing Knowledge (DEREK) nexus. (2019).marketed by LHASA Ltd Leeds Yorkshire UK DEREK Version Derek: 3.0.1; Nexus."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.13040\/ijpsr.0975-8232"},{"key":"e_1_2_6_5_1","unstructured":"Genotoxic and Carcinogenic impurities in Drug Substances and products. (2008).US Department of Health and Human services Rockville MD."},{"issue":"5","key":"e_1_2_6_6_1","first-page":"733","article-title":"Colesevelam hydrochloride: Reducing atherosclerotic coronary heart disease risk factors","volume":"3","author":"Harold B.","year":"2007","journal-title":"Vascular Health and Risk Management"},{"key":"e_1_2_6_7_1","unstructured":"International Conference on Harmonisation (ICH). (2017).Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk M7."},{"key":"e_1_2_6_8_1","unstructured":"International Conference on Harmonization (ICH). (2005).Validation of analytical procedures: Text and methodology Q2 (R1). The international conference on harmonization Geneva Switzerland.www.ich.org\/page\/quality-guidelines"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1201\/b17350-3"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40543-020-00254-2"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/op8002129"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/jpba.2014.01.009"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmy089"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/jpba.2013.11.013"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matpr.2020.03.102"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201401143"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c190007"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c00982"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmw070"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/jpba.2009.06.022"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5528","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.5528","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T23:19:16Z","timestamp":1760051956000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.5528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,29]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/bmc.5528"],"URL":"https:\/\/doi.org\/10.1002\/bmc.5528","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,29]]},"assertion":[{"value":"2022-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5528"}}