A quantitative testing method was developed for the analysis of low molecular weight (small molecules) nitrosamine impurities in cough syrups using solid phase extraction (SPE) on strong cation-exchange functionalized polymeric sorbent cartridges followed by gas chromatography-mass spectrometry. The matrix spike recoveries of the nitrosamine impurities from the cough syrup samples was observed to be within the range of 90 %-120 %. Limit of detection (LOD) achieved for NNitrosodimethylamine (NDMA) and NNitroso morpholine (NMOR) was about 0.1 ng/mL while the LOD for NNitrosodiethylamine (NDEA), NNitrosodiisopropylamine (NDIPA) and NNitrosoisopropylethylamine (NIPEA) impurities was about 0.02 ng/mL. The method was evaluated and found to meet the acceptable criteria as per the ICH Q2 guidelines for a working concentration range of 0.02 ng/mL to 1.2 ng/mL for the analyzed impurities. The selectivity of the nitrosamine impurities against the presence of drug product was established using multiple reaction monitoring (MRM) transitions during analysis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.chroma.2024.465148 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Based on the biologically active heterocycle quinoline, we successfully synthesized a series of quinoline-based dihydrazone derivatives (3a-3d). H NMR, C NMR, ESI-HRMS, IR, element analysis, UV/Vis spectroscopy and fluorescence spectroscopy were performed to comprehensively characterize their chemical structures, spectral properties and stability. Nitrosamine impurities were not detected in 3a-3d, and the systemic toxicological assessment indicated that the toxicity of 3a-3d was lower.
View Article and Find Full Text PDFThe 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 PDFCritical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.
Arch Toxicol
January 2025
Institute of Life Science, Swansea University Medical School, Swansea, UK.
The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.
View Article and Find Full Text PDFOptical and Electrical Dual-Mode Detection of a Carcinogenic Substance Based on Synergy of Liquid Crystals and Ionic Liquids.
ACS Sens
January 2025
School of Materials Science and Engineering, Tongji University, Shanghai 201804, P. R. China.
Visual, sensitive, and selective detection of carcinogenic substances is highly desired in portable health protection and practical medicine production. However, achieving this goal presents significant challenges with the traditional single-mode sensors reported so far, as they have limited sensing mechanisms and provide only a single output signal. Here, we report an effective optical and electrical dual-mode sensor for the visual, sensitive, and selective detection of -nitrosodiethylamine (NDEA), a typical volatile carcinogenic substance, leveraging the synergy of ionic liquid-doped liquid crystals (IL-LC).
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 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!