{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:54Z","timestamp":1787807934596,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":20,"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":["J of Separation Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nitrite impurities are frequently present in pharmaceutical excipients as a result of raw material sources and manufacturing processes. These impurities are of regulatory concern because nitrite can react with secondary amines to form nitrosamines, a class of potentially mutagenic compounds, making effective control of nitrite critical to ensuring the safety of pharmaceutical products. Current industrial methods for nitrite detection and quantification, such as ion chromatography and related techniques, are often limited by aqueous solvent compatibility, matrix dependence, or restricted instrument availability, which can hinder routine implementation across diverse pharmaceutical materials. In this study, a fast and sensitive analytical approach was developed to address these limitations by enabling nitrite quantification across excipients spanning a broad range of hydrophilicity to hydrophobicity. The method employs a newly developed nitrite isolation strategy from solid pharmaceutical excipient matrices, followed by rapid derivatization to form a UV\u2010active species that can be selectively quantified using high\u2010performance liquid chromatography with ultraviolet detection (HPLC\u2010UV). The resulting workflow demonstrates robust performance for low\u2010level nitrite detection while maintaining compatibility with standard HPLC instrumentation across the diverse ranges of tested pharmaceutical ingredients. The widespread availability of HPLC systems, combined with the method's rapid response, selectivity, and low detection limits for nitrite, supports its adoption for routine analytical control. This approach, therefore, provides a practical tool for nitrite monitoring and mitigation of nitrosamine formation risk in pharmaceutical formulations.<\/jats:p>","DOI":"10.1002\/jssc.70512","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:52:18Z","timestamp":1787374338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishing a Robust High Performance Liquid Chromatography\u2212Ultraviolet Detection Technique for Nitrite Quantification in Pharmaceutical Excipients and Active Pharmaceutical Ingredients"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6185-3187","authenticated-orcid":false,"given":"Kelly","family":"Blundin","sequence":"first","affiliation":[{"name":"Small Molecule Analytical Research and Development Merck &amp; Co. Inc.  Rahway New Jersey USA"},{"name":"Technical Development Moderna Inc.  Norwood Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-9896","authenticated-orcid":false,"given":"Syamantak","family":"Roy","sequence":"additional","affiliation":[{"name":"Small Molecule Analytical Research and Development Merck &amp; Co. Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Mularz","sequence":"additional","affiliation":[{"name":"Small Molecule Analytical Research and Development Merck &amp; Co. Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-3754","authenticated-orcid":false,"given":"Junyong","family":"Jo","sequence":"additional","affiliation":[{"name":"Small Molecule Analytical Research and Development Merck &amp; Co. Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02120"},{"key":"e_1_2_11_3_1","unstructured":"\u201cRecalls of Angiotensin II Receptor Blockers (ARBs) Including Valsartan Losartan and Irbesartan \u201d U.S. Food and Drug Administration accessed May 4 2026 https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/recalls\u2010angiotensin\u2010ii\u2010receptor\u2010blockers\u2010arbs\u2010including\u2010valsartan\u2010losartan\u2010and\u2010irbesartan."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2023.12.009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2023.01.028"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.3c00100"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.0c02774"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.0c00224"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.3c00153"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.38212\/2224-6614.3400"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2022.11.013"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(75)90255-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2026.107516"},{"key":"e_1_2_11_14_1","unstructured":"\u201cAssessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7(R2)\u201d International Council for Harmonisation (ICH) accessed May 4 2026 https:\/\/efaidnbmnnnibpcajpcglclefindmkaj\/https:\/\/database.ich.org\/sites\/default\/files\/ICH_M7(R2)_Guideline_Step4_2023_0216_0.pdf."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15082015"},{"key":"e_1_2_11_16_1","first-page":"1614","article-title":"Assessment of Nitrite and Nitrate Sources in Pharmaceutical Excipients and Their Role in N\u2010Nitrosamine Formation","volume":"24","author":"Teasdale A.","year":"2020","journal-title":"Organic Process Research and Development"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2025.107236"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202300125"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201600093"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.70134"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2022.132280"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(03)00735-0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.4c00037"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/app14199027"},{"key":"e_1_2_11_25_1","first-page":"424","article-title":"Ion Chromatography: Fundamentals and Applications in Environmental and Pharmaceutical Analysis","volume":"85","author":"Dasgupta P. 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