TY - JOUR
T1 - A comprehensive review of sources of nitrosamine contamination of pharmaceutical substances and products
AU - Akkaraju, Harshita
AU - Tatia, Ritik
AU - Mane, Sayalee Sanjay
AU - Khade, Amol B.
AU - Dengale, Swapnil J.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/3
Y1 - 2023/3
N2 - N-nitrosamines are carcinogenic impurities most commonly found in groundwater, treated water, foods, beverages and consumer products. The recent discovery of N-nitrosamines in pharmaceutical products and subsequent recalls pose a significant health risk to patients. Initial investigation by the regulatory agency identified Active Pharmaceutical Ingredients (API) as a source of contamination. However, N-nitrosamine formation during API synthesis is a consequence of numerous factors like chemistry selection for synthesis, contaminated solvents and water. Furthermore, apart from API, N-nitrosamines have also been found to embed in the final product due to degradation during formulation processing or storage through contaminated excipients and printing inks. The landscape of N-nitrosamine contamination of pharmaceutical products is very complex and needs a comprehensive compilation of sources responsible for N-nitrosamine contamination of pharmaceutical products. Therefore, this review aims to extensively compile all the reported and plausible sources of nitrosamine impurities in pharmaceutical products. The topics like risk assessment and quantitative strategies to estimate nitrosamines in pharmaceutical products are out of the scope of this review.
AB - N-nitrosamines are carcinogenic impurities most commonly found in groundwater, treated water, foods, beverages and consumer products. The recent discovery of N-nitrosamines in pharmaceutical products and subsequent recalls pose a significant health risk to patients. Initial investigation by the regulatory agency identified Active Pharmaceutical Ingredients (API) as a source of contamination. However, N-nitrosamine formation during API synthesis is a consequence of numerous factors like chemistry selection for synthesis, contaminated solvents and water. Furthermore, apart from API, N-nitrosamines have also been found to embed in the final product due to degradation during formulation processing or storage through contaminated excipients and printing inks. The landscape of N-nitrosamine contamination of pharmaceutical products is very complex and needs a comprehensive compilation of sources responsible for N-nitrosamine contamination of pharmaceutical products. Therefore, this review aims to extensively compile all the reported and plausible sources of nitrosamine impurities in pharmaceutical products. The topics like risk assessment and quantitative strategies to estimate nitrosamines in pharmaceutical products are out of the scope of this review.
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U2 - 10.1016/j.yrtph.2023.105355
DO - 10.1016/j.yrtph.2023.105355
M3 - Review article
C2 - 36792049
AN - SCOPUS:85148633737
SN - 0273-2300
VL - 139
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
M1 - 105355
ER -
