{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:27:29Z","timestamp":1790702849830,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100014824","name":"Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2024,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>\n                      <jats:italic>N<\/jats:italic>\n                      \u2010Nitroso dimethylamine (NDMA) is a mutagenic impurity detected in several ranitidine products. The amino functional group of ranitidine is a risk factor for classical nitrosation\u2010induced NDMA formation in ranitidine drug products during storage conditions. The United States Food and Drug Administration (US FDA) recommended the use of antioxidants to control NDMA in drug products. Considering the need for sensitive analytics, a liquid chromatography\/high\u2010resolution mass spectrometry (LC\u2013HRMS) method was developed and validated to detect NDMA in this pilot study to demonstrate the antioxidants as inhibitors of nitrosation reactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The method, utilizing an EC\u2010C18 column and tuned to atmospheric pressure chemical ionization\/selected ion monitoring (APCI\/SIM) mode, separated NDMA (\n                      <jats:italic>m\/z<\/jats:italic>\n                      : 75.0553; tR: 3.71\u2009min) and ranitidine (\n                      <jats:italic>m\/z<\/jats:italic>\n                      : 315.1485; tR: 8.61\u2009min). APCI mode exhibited four times higher sensitivity to NDMA than electrospray ionization (ESI) mode. Classical nitrosation of the dimethyl amino group of ranitidine was studied with sodium nitrite in solid pellets. Antioxidants (alpha\u2010tocopherol, ascorbic acid, and trolox) were evaluated as NDMA attenuators in ranitidine pellets under vulnerable storage conditions. The developed method quantified NDMA levels in samples, extracted with methanol through vortex shaking for 45 min.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The method achieved a limit of detection (LOD) and limit of quantitation (LOQ) of 0.01 and 0.05\u2009ng\/mL, respectively, with linearity within 1\u20135000\u2009ng\/mL (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>1<\/jats:sup>\n                      : 0.9995). It demonstrated good intra\u2010day and inter\u2010day precision (% RSD [relative standard deviation]: &lt;2) and accuracy (96.83%\u2013101.72%). Nitrosation of ranitidine induced by nitrite was significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001;\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.9579) at various sodium nitrite levels. All antioxidants efficiently attenuated NDMA formation during ranitidine nitrosation. Ascorbic acid exhibited the highest NDMA attenuation (96.98%), followed by trolox (90.58%). This study recommends 1% ascorbic acid and trolox as potent NDMA attenuators in ranitidine drug products.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study compared the effectiveness of antioxidants as NDMA attenuators in ranitidine under storage conditions susceptible to NDMA generation. The study concluded that ascorbic acid and trolox are potent inhibitors of NDMA formation and nitrosation attenuators in ranitidine drug products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.9747","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:30:38Z","timestamp":1712795438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development and validation of high\u2010performance liquid chromatography\u2010Orbitrap mass spectrometric method for quantification of NDMA in ranitidine drug products and evaluation of antioxidants as inhibitors of classical nitrosation reaction"],"prefix":"10.1002","volume":"38","author":[{"given":"Dande","family":"Aishwarya","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research (NIPER)  Hajipur Bihar 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