NAVIGATING NITROSAMINES: ORIGIN, DETECTING, ANALYSING AND REGULATING IMPURITIES IN PHARMACEUTICALS

TEJAS SANJAY SONAWANE; TANVI PAINGINKAR; RUCHIR BAVADIA; SG VASANTHARAJU; MUDDUKRISHNA BADAMANE SATHYANARAYANA; GUNDAWAR RAVI

doi:10.22159/ijap.2024v16i5.51376

Authors

TEJAS SANJAY SONAWANE Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104. Karnataka, India. https://orcid.org/0000-0002-6253-4935
TANVI PAINGINKAR Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104. Karnataka, India.
RUCHIR BAVADIA Dr. Reddy’s, Hyderabad-500090. Telangana State, India https://orcid.org/0000-0002-4041-0560
SG VASANTHARAJU Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104. Karnataka, India.
MUDDUKRISHNA BADAMANE SATHYANARAYANA Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104. Karnataka, India.
GUNDAWAR RAVI Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104. Karnataka, India

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51376

Keywords:

N-nitrosamines, Impurities, Analytical techniques, Recall, Detection, Quantification, Regulatory

Abstract

N-nitrosamines are carcinogenic impurities mostly found in groundwater, treated water, foods, beverages, and consumer products like processed meats, alcoholic beverages, cosmetics, and cigarette smoke. The recent discovery of N-nitrosamines in pharmaceutical products and subsequent recalls pose a significant health risk to patients. Nitrosamine impurities in drug products have appeared as a critical concern in pharmaceuticals prompting extensive scrutiny from regulatory agencies and stakeholders. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control acceptable limits for nitrosamine impurities in pharmaceuticals. This review provides an information on historical background of Nitrosamine impurities; its carcinogenic effect; the sources and formation of impurities; associated risks of nitrosamines in drug formulations; different analytical techniques for nitrosamine detection. It also gives an understanding of the general Quality Risk management (QRM) process, techniques for measuring nitrosamine impurities with control strategies as directed by the regulatory authorities and how to avoid them in pharmaceutical drug products. A brief review on recalls of drug classes including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs by regulatory bodies due to its potential harm produced by nitrosamine have been discussed. Moreover, the regulatory landscape governing nitrosamine impurities are explored, encompassing recent guidelines from major regulatory bodies such as the United States Food and Drug Administration (USFDA), European Medicines Agency (EMA) and Health Canada (HC) in controlling/eliminating the nitrosamine impurities in pharmaceuticals.

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