Nitrosamine impurities, particularly N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), have emerged as critical safety concerns in pharmaceutical products due to their potent carcinogenic nature. The present study focuses on the development of an advanced and sensitive analytical method for the detection and quantification of these impurities in active pharmaceutical ingredients and finished dosage forms.

A robust analytical method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed and validated. The method exhibited excellent linearity over the concentration range of 0.5–100 ng/mL with correlation coefficients (R²) of 0.9992 for NDMA and 0.9990 for NDEA. The limits of detection (LOD) were found to be 0.15 ng/mL for NDMA and 0.20 ng/mL for NDEA, while the limits of quantification (LOQ) were 0.50 ng/mL and 0.65 ng/mL, respectively. The method demonstrated high accuracy with recovery values ranging from 98.2% to 101.2% for NDMA and 97.5% to 102.0% for NDEA. Precision studies showed %RSD values below 5%, indicating excellent reproducibility.

The developed method was successfully applied to pharmaceutical samples, where NDMA and NDEA were either not detected or found at trace levels within acceptable regulatory limits. The use of isotopically labeled internal standards effectively minimized matrix effects and improved quantification accuracy.

In conclusion, the proposed method is highly sensitive, reliable, and suitable for routine quality control analysis of nitrosamine impurities in pharmaceutical products. It provides a strong analytical platform for ensuring regulatory compliance and offers potential for future expansion to multi-nitrosamine analysis.