Advancing Green Analytical Chemistry: LC–MS/MS Method Development for Ultra-Trace Nitrosamine and Genotoxic Impurity Control

Nitrosamines/GTIs challenge pharmaceutical safety at trace levels. This study
develops/validates a green LC–MS/MS method for ultra-trace detection/quantification of
selected nitrosamines/GTIs, emphasizing reduced solvent use, eco-friendly phases, and
simplified preparation. Short C18 column with gradient elution achieved separation; MRM
mode ensured sensitivity/selectivity. Linearity spanned low-ppb range; LOD/LOQ beat
regulatory limits. Validation confirmed accuracy, precision, specificity, robustness. It merges
green chemistry with compliance for routine monitoring. Green preparation minimized
handling/solvents: weigh/dissolve/filter drug substances/dosage forms; use certified
standards. Employed HPLC water, judicious ethanol/acetonitrile, ammonium formate/acetate
buffers. LC–MS/MS with short C18 column, aqueous buffer + low organic modifier under
optimized gradient for short runtime. Outperforms conventional methods by slashing solvent
use, time, and waste; MS-compatible low-toxicity solvents sustain analysis without
performance loss.
Keywords: Green analytical chemistry; LC–MS/MS; Nitrosamines; Genotoxic impurities