Answers are grounded in this paper and cite their sources.
The presence of N-nitrosamine impurities in pharmaceutical products, even at ultra-trace levels, has emerged as a major regulatory and public health concern because of their carcinogenic risk. In this study, a robust, ultrasensitive, and environmentally sustainable LC–MS/MS method was developed and validated for the simultaneous determination of three critical nitrosamine impurities: N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitroso-N-methyl-4-aminobutyric acid (NMBA). The method was successfully applied to determine of these nitrosamines in pharmaceutical formulations containing albendazole, sotalol HCl, and nalbuphine HCl. Chromatographic separation was achieved using Eclipse Plus C8 (4.6 × 250 mm) and Kinetex® F5 (4.6 × 100 mm) columns with gradient elution using 0.1% formic acid in water and methanol. The proposed method provided efficient separation within 9 min at a flow rate of 0.6 mL/min and a column temperature of 40 °C. Validation was performed according to ICH guidelines, demonstrating excellent linearity (r > 0.99), good precision, accuracy, selectivity, and specificity. The validated linearity ranges were 1–25 ng/mL for albendazole, 0.25–100 ng/mL for sotalol HCl and nalbuphine HCl, with limits of quantification as low as 1 ng/mL. Recoveries ranged from 70.9% to 116.1%. In silico ADMET analysis indicated potential hepatotoxicity risks for all investigated nitrosamines, emphasizing the importance of continuous monitoring. Furthermore, the method demonstrated strong green analytical performance, with BAGI scores of 75.0–77.5 and AGREE values of 0.58–0.60. The developed LC–MS/MS method offers a sensitive, reliable, and environmentally sustainable approach for routine monitoring of nitrosamine impurities in pharmaceutical formulations for quality control purposes. Validated sensitive LC–MS/MS method for simultaneous determination of NDMA, NDEA, and NMBA in pharmaceutical formulations.Fast, accurate, and highly selective analysis with ng/mL sensitivity suitable for regulatory quality control.Integrated green analytical chemistry assessment with in silico ADMET profiling for comprehensive evaluation of nitrosamine impurities. Validated sensitive LC–MS/MS method for simultaneous determination of NDMA, NDEA, and NMBA in pharmaceutical formulations. Fast, accurate, and highly selective analysis with ng/mL sensitivity suitable for regulatory quality control. Integrated green analytical chemistry assessment with in silico ADMET profiling for comprehensive evaluation of nitrosamine impurities.
No takes yet. Share an insight, caveat, or question.
Saeed et al. (2026) studied this question.