Development and Validation of Analytical Methods for the Quantification and Identification of N-Nitroso Trimetazidine, a Nitrosamine Impurity, in Drug Substance and Drug Product.

Development and Validation of Analytical Methods for the Quantification and Identification of N-Nitroso Trimetazidine, a Nitrosamine Impurity, in Drug Substance and Drug Product. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 February 2025 V1 Latest version Share on Development and Validation of Analytical Methods for the Quantification and Identification of N-Nitroso Trimetazidine, a Nitrosamine Impurity, in Drug Substance and Drug Product. Authors : Sandip Vadariya 0009-0008-0259-3512 , Jigar Patel [email protected] , Haresh Patel , and Hitin Hirpara Authors Info & Affiliations https://doi.org/10.22541/au.173924857.76644661/v1 472 views 140 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract RATIONALE In the manufacturing process of Trimetazidine hydrochloride (TMZ), N Nitroso trimetazidine (NTMZ) generate, final purification of active pharmaceutical ingredient (API) done in the presence of the charcoal, which has been identified as a possible source of nitrite. Secondary amine is present in TMZ, due to the favorable condition for nitrosamine & NDSRIs, NTMZ is generated in TMZ. Significant genotoxic and mutagenic effects of NDSRIs effect on human and regulatory requirement to control. METHODS This study is held for the trace level identification and quantification of NTMZ in TMZ drug substance and in drug product by using ultra-fast liquid chromatography-mass spectrometry/mass spectrometry (UFLC-ESI-MS/MS). The method was developed and validated for the NTMZ content in gradient mode using inert Sustain PFP (4.6 mm x 150 mm x 5 µ) column, a buffer containing 0.63 g/L ammonium formate in water and 1 mL formic acid as solution A and while solution B a mixture of methanol and acetonitrile in the ratio of 50:50 (v/v). Positive ionization in electrospray ionization (ESI) with MRM ( m/z 296.15 > 181.15, 296.15 > 166.05, 296.15 > 136.15) used for NTMZ quantification and identification. RESULTS The limit of detection and Quantification 0.16 ppm and 0.50 ppm respectively. The method is linear in the range of 0.5 ppm to 7.5 ppm (0.00025 ppm to 0.00375 ppm). System precision (% RSD= 4.47), Method precision (% RSD = 1.92), Intermediate precision (% RSD = 2.47), Accuracy (77.7 – 126.85 %). CONCLUSIONS To identify and quantify the trace level NTMZ in commercial drug substances and drug products, this validated analytical method was effectively applied. As the knowledge this is the first method to identify and quantify NTMZ with UPLC-ESI-MS/MS and no comparable techniques. Supplementary Material File (n-nitroso trimetazidine_research paper_sandip vadariya.docx) Download 337.05 KB Information & Authors Information Version history V1 Version 1 11 February 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords analytical methods & validation lc-ms/ms mrm ndsris nitrosamine trimetazidine Authors Affiliations Sandip Vadariya 0009-0008-0259-3512 Cohance Lifesciences Limited API R&D Centre View all articles by this author Jigar Patel [email protected] Sophisticated Instrumentation Centre for Applied Research and Testing – SICART View all articles by this author Haresh Patel Cohance Lifesciences Limited API R&D Centre View all articles by this author Hitin Hirpara Cohance Lifesciences Limited API R&D Centre View all articles by this author Metrics & Citations Metrics Article Usage 472 views 140 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Sandip Vadariya, Jigar Patel, Haresh Patel, et al. Development and Validation of Analytical Methods for the Quantification and Identification of N-Nitroso Trimetazidine, a Nitrosamine Impurity, in Drug Substance and Drug Product.. Authorea . 11 February 2025. DOI: https://doi.org/10.22541/au.173924857.76644661/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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