Development and Validation of a Sensitive GC-MS Method for Determination of Nitrosamine Impurities in Foscarnet Sodium Injection

Abstract

Nitrosamine impurities are an important pharmaceutical quality concern because several members of this chemical class possess mutagenic and carcinogenic potential. The present study focused exclusively on the GC-MS component of the Ph.D. work and evaluated selected nitrosamine impurities in Foscarnet Sodium Injection. The investigated nitrosamines were N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), and N-nitrosodibutylamine (NDBA). A DB-1701 column (30 m × 0.25 mm, 1 μm) was used with helium carrier gas at 1.0 mL/min, an injector temperature of 250°C, electron-impact ionization, 2.0 μL injection volume, and a total run time of 12.33 min. Method validation included specificity, linearity, accuracy, precision, LOD, LOQ, robustness, and system suitability. No interfering peaks were observed in solvent blank and placebo, while clear peaks were obtained for NDMA, NDEA, NDIPA, and NDBA. The GC-MS calibration range was 5–100 ng/mL. Representative NDMA linearity gave y = 2487x + 215 with r² = 0.9989. The reported LOD was 1–3 ng/mL and LOQ was 5 ng/mL. NDMA recovery at 50%, 100%, and 150% levels was 94.0%, 95.5%, and 96.7%, with %RSD values of 7.8%, 6.2%, and 5.4%, respectively. Repeatability was within the stated acceptance limit and no significant variation was observed under deliberate parameter changes. The developed GC-MS method therefore demonstrated sensitivity and selectivity suitable for trace-level nitrosamine analysis in Foscarnet Sodium Injection.