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{"references": ["Antonis Manolis (April 26, 2019), \"Carcinogenic Impurities in Generic Sartans: An Issue of Authorities' Control or a Problem with Generics\", Rhythmos; Volume 14, Issue 2, pp.23-26. DOI: 10.1021/cen-09708.", "FDA Press Release (July, 2018), \"FDA announces voluntary recall of several medicines containing valsartan following detection of an impurity,\" APHA.", "EMA Press Release (September 21, 2018), \"Valsartan: Review of Impurities Extended to Other Sartan Medicines,\" EMA, Available at https://www.ema.europa.eu.", "Jennifer L. Caulfield (1997), \"The chemistry of nitric oxide-induced deamination and cross-linking of DNA\", (Doctoral dissertation), Massachusetts Institute of Technology, pp. 1-153.", "R. Nilsson (July, 2011), \"The molecular basis for induction of human cancers by tobacco specific nitrosamines\", Regulatory Toxicology and Pharmacology, Volume 60, Issue 2, pp. 268-80. Available at https://doi.org/10.1016/j.yrtph.2011.02.014.", "Lijinsky W. Andrews AW. (October, 1983), \"The superiority of hamster liver microsomal fraction for activating nitrosamines to mutagens in Salmonella typhimurium\", Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. Volume 111, Issue 2, pp.135-144. DOI: 10.1016/0027-5107(83)90058-1.", "Aloka Srinivasan (2019), \"Proactive Evaluation of Possible Genotoxic Impurities during the Early Stages of Drug Development\", http://www.pharmtech.com.", "G. Subba Rao (1980), \"N-Nitrosarnines from drugs and nitrite: potential source of chemical carcinogens in humans\", Pharmacy International, Volume 1, pp. 187-190.", "\"Information on nitrosamines for marketing authorization holders\", European Medicines Agency, pp. 1-10, EMA/CHMP/428592/2019 Rev. 2.", "U. S. Food and Drug Administration update (Jan 25, 2019), \"Statement on the FDA's ongoing investigation into valsartan and ARB class impurities and the agency's steps to address the root causes of the safety issues\", https://www.fda.gov."]}
Nitrosamine impurities are known to be mutagenic and carcinogenic, very small exposure of these impurities can lead to cancer. These impurities may be formed and get incorporated into drug substance or drug product through reagent, catalyst, solvent or raw materials used in the process of manufacturing. The various regulatory authority has published the press release or notice regarding the control of these impurities with the interim limit. Nitrosamine impurities can be avoided by taking precaution in the manufacturing of drug substance and drug products. Validated analytical methods are to be used to identify and quantify these impurities hence it needs highly sensitive instrument which can detect these impurities to the trace level at given interim limit. Liquid chromatography or Gas chromatography, along with mass detector is majorly used for their determination.
Classification, drug substances, drug product, impurities, nitrosamine and guidelines, http://matjournals.com/Pharmacy-Journals.html
Classification, drug substances, drug product, impurities, nitrosamine and guidelines, http://matjournals.com/Pharmacy-Journals.html
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