Nitrosamine Impurities In Pharmaceuticals: A Comprehensive Review

Abstract

When several nitrosamine impurities are found and their cumulative amount surpasses 26.5 ng/day (which is the maximum daily dose (MDD) allowable consumption for the nitrosamine), the FDA asks the producers to get in touch with them so they may conduct an assessment. When evaluating the risk of human cancer, controlling potentially mutagenic contaminants in pharmaceutical products and crucial interest in the mutagenic and carcinogenic potential of nitrosamine impurities has grown since they were recently found in several medicinal products that are commercialized. A "Cohort of Concern" for which the chemical class is deemed to belong indicates that some common control procedures, including using the threshold of toxicological concern (TTC), cannot be used.

These contaminants were in the pharmaceutical products throughout the production process via raw materials, catalysts, and solvents. By altering the production process or taking safety measures while producing drug products, nitrosamine impurities can be prevented.

To identify and characterize these contaminants validated analytical methods are applied. Mass spectrometry, liquid chromatography, and gas chromatography are the analytical techniques. These impurities originated from the first time a nitrosating agent was used in secondary, tertiary, and ammonium salt. These techniques aid in maintaining a low concentration of nitrosamine contaminants in a drug or drug product intended for use in human medicine.