{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T18:35:15Z","timestamp":1784399715416,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Residual solvents, or organic volatile impurities, are a potential toxic risk for pharmaceutical products and have been a manufacturers\u2019 concern for many years. Moreover, residual solvents can also affect the quality and stability of not only drug substances but also of drug products. The objective of this work is the development and validation of headspace gas chromatographic method for determination of six residual solvents (methanol, ethyl acetate, isopropyl alcohol, triethylamine, chloroform, and toluene) in losartan potassium raw material. Method development evaluated the critical parameters of sample diluent selection (dimethylsulfoxide and water), optimization of headspace conditions (incubation time and temperature), and chromatographic conditions (column temperature ramp speeds and sample split ratio). Validation was carried out in accordance to Brazilian guidelines. Dimethylsulfoxide was selected as the sample diluent, with an incubation time of 30\u00a0min at 100\u00b0C. The chromatographic determination was performed on a DB\u2010624 capillary column using programmed temperature, running time of 28\u00a0min and a split ratio of 1:5. The method proved to be selective, with suitable sensitivity (limits of quantification below 10% of the specification limits determined by the ICH), precise (relative standard deviations\u00a0\u2264\u00a010.0%), linear (\n                    <jats:italic>r<\/jats:italic>\n                    \u00a0\u2265\u00a00.999 for all solvents\u2019 standard curves), accurate (average recoveries from 95.98% to 109.40%), and robust under the small modifications in the chromatographic conditions. A simple and reliable method was obtained. The analysis of a losartan potassium raw material batch has detected only isopropyl alcohol and triethylamine as residual solvents, indicating that purification processes applied to this active pharmaceutical ingredient production were capable to remove most solvents from synthesis step.\n                  <\/jats:p>","DOI":"10.1002\/jssc.70319","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T16:06:56Z","timestamp":1763050016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analytical Method by Headspace\u2010Gas Chromatography for Determination of Six Residual Solvents in Losartan Potassium Raw Material"],"prefix":"10.1002","volume":"48","author":[{"given":"Vanessa B.","family":"de Camargo","sequence":"first","affiliation":[{"name":"Programa De P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas (PPGCF), Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande Do Sul (UFRGS). Av. Ipiranga, Porto  Alegre\/RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssia V.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Programa De P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas (PPGCF), Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande Do Sul (UFRGS). Av. Ipiranga, Porto  Alegre\/RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/pt030206"},{"key":"e_1_2_8_3_1","unstructured":"International Council on Harmonisation of Technical Requirements for Registration of Pharmaceutical for Human Use \u201cImpurities in New Drug Substances Q3A(R2) \u201d published October 25 2006 https:\/\/database.ich.org\/sites\/default\/files\/Q3A%28R2%29%20Guideline.pdf."},{"key":"e_1_2_8_4_1","first-page":"46","volume-title":"General Tests, 2.46 Residual Solvents","author":"Japanese Pharmacopoeia","year":"2021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2015.09.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201100051"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201100917"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02492813"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2004.09.055"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2010.01.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.06.020"},{"key":"e_1_2_8_12_1","volume-title":"Residual Solvents\u2014Verification of Compendial Procedures and Validation of Alternative Procedures","author":"United States Pharmacopoeia","year":"2022"},{"key":"e_1_2_8_13_1","volume-title":"Identification and Control of Residual Solvents","author":"European Pharmacopoeia","year":"2022"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2023.101269"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2020.06.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200500430"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202300018"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201801024"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202100048"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0731\u20107085(03)00347\u20109"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00100a048"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/op300179u"},{"key":"e_1_2_8_23_1","unstructured":"BRASIL. Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria. Resolu\u00e7\u00e3o da Diretoria Colegiada\u2014RDC n\u00b0166 de 24 de julho de 2017. Dispoe sobre a validacao de metodos analiticos e da outras providencias. Di\u00e1rio Oficial da Rep\u00fablica Federativa do Brasil (2017) Bras\u00edlia."},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007690050359"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2004.09.023"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2004.06.014"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1365\/s10337\u2010004\u20100211\u20102"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.05.015"}],"container-title":["Journal of Separation Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.70319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T05:43:24Z","timestamp":1765259004000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jssc.70319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":27,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jssc.70319"],"URL":"https:\/\/doi.org\/10.1002\/jssc.70319","archive":["Portico"],"relation":{},"ISSN":["1615-9306","1615-9314"],"issn-type":[{"value":"1615-9306","type":"print"},{"value":"1615-9314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70319"}}