In the last decade a considerable effort has been made both by the regulators and the pharmaceutical industry to assess genotoxic impurities (GTI) in pharmaceutical products. Though the control of impurities in drug substances and products is a well established and consolidated procedure, its extension to GTI has given rise to a number of problems, both in terms of setting the limits and detecting these impurities in pharmaceutical products. Several papers have dealt with this issue, discussing available regulations, providing strategies to evaluate the genotoxic potential of chemical substances, and trying to address the analytical challenge of detecting GTI at trace levels. In this review we would like to discuss the available regulations, the toxicological background for establishing limits, as well as the analytical approaches used for GTI assessment. The final aim is that of providing a complete overview of the topic with updated available information, to address the overall GTI issue during the development of new drug substances.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejps.2011.03.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Presence of Nitrosamines and Nitrosamine Drug-Related Substances in Pharmaceutical Products: An Overview of Regulatory Concerns, Analytical Methodologies, and Control Strategies.
Curr Drug Saf
January 2025
Department of Chemistry, K J Somaiya College of Science and Commerce, Vidyavihar, Mumbai-77, India.
The presence of N-nitrosamine impurities in pharmaceutical products is well known. In 2019, it resulted in drug recall by the Food and Drug Administration (FDA). Soon, several groups identified the presence of many N-nitrosamines (NAs) in various Active Pharmaceutical Ingredients (APIs) and drug formulations worldwide.
View Article and Find Full Text PDFMachine learning enhances genotoxicity assessment using MultiFlow® DNA damage assay.
Environ Mol Mutagen
December 2024
Research and Development, Preclinical Safety, Sanofi, Industriepark Hoechst, Frankfurt am Main, Germany.
Genotoxicity is a critical determinant for assessing the safety of pharmaceutical drugs, their metabolites, and impurities. Among genotoxicity tests, mechanistic assays such as the MultiFlow® DNA damage assay (MFA) allows the investigations on mode of action (MoA) of DNA damage through four mechanistic markers recorded at two time points. Previous studies have shown that machine learning (ML) can enhance precision on classifying the MoA of genotoxicants.
View Article and Find Full Text PDFChromatographic Separation and Quantification of Nine Nitrosamine Genotoxic Impurities in a Single Method in Nebivolol Tablet by Using Validated Ultra-Sensitive Liquid Chromatography: Mass Spectrometry Analytical Method.
J Chromatogr Sci
January 2025
Analytical Research Laboratory, Cadila Pharmaceuticals Ltd., Dholka, Ahmedabad 382225, India.
N-nitrosamine impurities have been detected in a vast variety of drug substances and drug products, showing concern for regulatory aspects. To meet the regulatory requirement for the concerned impurity, a sensitive analytical method capable of quantifying these impurities at a lower level with accuracy and precision is required. This article focuses on the development and validation of an analytical method for the simultaneous detection of nine nitrosamine impurities in a single method for nebivolol drug product using liquid chromatography-mass spectrometry/mass spectrometry-atmospheric pressure chemical ionization (LC-MS/MS-APCI).
View Article and Find Full Text PDFThe EFSA Panel on Food Contact Materials assessed the safety of 2,2'-oxydiethylamine, which is intended to be used at up to 14% w/w as a monomer along with adipic acid and caprolactam to make polyamide thin films intended for single use, in contact with all types of food under all conditions of time and temperature. Specific migration of 2,2'-oxydiethylamine was tested from a polyamide film in water and was below the limit of quantification (LOQ) of 0.015 mg/kg.
View Article and Find Full Text PDFThis opinion deals with the re-evaluation of saccharin and its sodium, potassium and calcium salts (E 954) as food additives. Saccharin is the chemically manufactured compound 1,2-benzisothiazol-3(2H)-one-1,1-dioxide. Along with its sodium (Na), potassium (K) and calcium (Ca) salts, they are authorised as sweeteners (E 954).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!