{"id":18517,"date":"2024-02-13T22:31:22","date_gmt":"2024-02-13T22:31:22","guid":{"rendered":"https:\/\/cqab.eu\/synthesis-and-analysis-of-nitrosamines\/"},"modified":"2024-05-21T19:14:39","modified_gmt":"2024-05-21T19:14:39","slug":"synthesis-and-analysis-of-nitrosamines","status":"publish","type":"post","link":"https:\/\/cqab.eu\/en\/synthesis-and-analysis-of-nitrosamines\/","title":{"rendered":"Synthesis and analysis of nitrosamines"},"content":{"rendered":"\t\t
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Since the so-called \"Nitrosamines (N-NAs) Crisis\" emerged in June 2018, the European<\/p>\n

Medicines Agency (EMA), and the Food and Drug Administration (FDA), together with the<\/p>\n

rest of the regulatory agencies, began to carry out risk analysis, in order to identify the<\/p>\n

different causes of the formation of these compounds and eradicate their presence, both in<\/p>\n

active ingredient and in finished product. And in order to respond to many of the needs that<\/p>\n

have arisen from these risk analyses, the Center for Applied Chemistry and Biotechnology<\/p>\n

(CQAB), within the Pilot Plant and Biotechnology Area, has focused on the synthesis,<\/p>\n

isolation and characterization of N-NAs and N-Nitroso compounds (NOCs) formed directly<\/p>\n

on the corresponding active ingredients (APIs). Until now, N-NAs have been obtained in<\/p>\n

active ingredients with great molecular diversity and application in different therapeutic<\/p>\n

areas. These API nitrosamines are being used as standards when quantified by NMR.<\/p>\n

Currently, several of the structures obtained are being used to address a large part of the<\/p>\n

problem of identifying N-NAs in APIs and finished products, thus favoring their correct<\/p>\n

pharmacovigilance.<\/p>\n

Moreover, a new ultra-sensitive analytical method based on the FDA method was developed using<\/p>\n

LC-MS\/MS with HRMS for the quantification of six nitrosamine (NAs) impurities in different<\/p>\n

drug substances (N-nitroso-dimethylamine, N-nitroso-diethylamine, N-nitroso-ethyl-isopropyl<\/p>\n

amine, N-nitroso-diisopropylamine, N-nitroso-dibutylamine, and N-nitroso-N-methyl-4-<\/p>\n

aminobutyric acid). This method improves the sensitivity of the FDA method up to about 20<\/p>\n

times, being also reduced the analysis time to the half. Its high sensitivity and easy sample<\/p>\n

treatment should be of relevance in the field of pharmaceutical quality control for determining<\/p>\n

NAs impurities associates to the synthesis processes. Moreover, for the detection of other possible<\/p>\n

nitrosamines formed as by-products due to the modification of the manufacturing processes, a<\/p>\n

screening method in full scan mode was also developed showing a deteccion limits similar to the<\/p>\n

FDA.<\/p>\n

Therefore, these two new methodologies provide a reliable method for routine control of<\/p>\n

nitrosamine impurities in pharmaceutical industry.<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Since the so-called “Nitrosamines (N-NAs) Crisis” emerged in June 2018, the European Medicines Agency (EMA), and the Food and Drug<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[92],"tags":[],"class_list":["post-18517","post","type-post","status-publish","format-standard","hentry","category-last-news"],"_links":{"self":[{"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/posts\/18517","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/comments?post=18517"}],"version-history":[{"count":4,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/posts\/18517\/revisions"}],"predecessor-version":[{"id":18521,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/posts\/18517\/revisions\/18521"}],"wp:attachment":[{"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/media?parent=18517"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/categories?post=18517"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cqab.eu\/en\/wp-json\/wp\/v2\/tags?post=18517"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}