The presence of nitrosamine impurities in pharmaceutical products has emerged as a significant safety concern due to their potential carcinogenic nature. In this study, a high-precision analytical method was developed and validated for the simultaneous detection and quantification of selected nitrosamines, including N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), N-nitrosoethylisopropylamine (NEIPA), and N-nitrosodibutylamine (NDBA), in pharmaceutical active ingredients and formulations. The method employed optimized extraction techniques combined with advanced LC–MS/MS and GC–MS/MS instrumentation to achieve high sensitivity and selectivity.

The developed method demonstrated excellent linearity over the concentration range of 0.5–100 ng/mL, with correlation coefficients (R²) greater than 0.999 for all analytes. The limits of detection ranged from 0.15 to 0.35 ng/mL, while limits of quantification were between 0.50 and 1.20 ng/mL, indicating the capability for ultra-trace analysis. Recovery studies showed accuracy within 95.5% to 102.0%, and precision studies yielded %RSD values below 5%, confirming the reproducibility of the method.

Application of the method to pharmaceutical samples revealed the presence of NDMA in the range of 1.2–3.0 ng/g, while other nitrosamines were either not detected or present at trace levels within acceptable regulatory limits. Matrix effect evaluation showed minimal ion suppression or enhancement, with matrix factor values ranging from 0.97 to 1.02.