Highly sensitive monitoring of genotoxic impurity 2-nitrobenzaldehyde in pharmaceutical formulations via...

2-Nitrobenzaldehyde (2-NBA), a key intermediate in the synthesis of nifedipine, is a potential genotoxic impurity that poses significant health risks even at trace levels. This study develops a novel solid-phase microextraction (SPME) method using a hyper-crosslinked polymer (HCP) as the coating material for the sensitive quantification of 2-NBA in pharmaceutical formulations. The HCP was synthesized via Friedel-Crafts alkylation using 3,6-dichlorocarbazole as the monomer and 4,4'-bis(chloromethyl)-1,1'-biphenyl as the crosslinker. The material exhibits high specific surface area, thermal stability, and effective adsorption capacity for 2-NBA, attributed to halogen bonding and other non-covalent interactions. The SPME-GC-FID method was optimized for key parameters, including extraction time, sample pH, ionic strength, and desorption conditions, achieving a limit of detection (LOD) of 8.9 pg mL^-1 and a limit of quantification (LOQ) of 29.6 pg mL^-1. The method demonstrated good linearity (r = 0.9996) and high recovery rates (84.5 %-99.4 %) for spiked samples, confirming its accuracy and reproducibility. This method was successfully applied to detect 2-NBA in nifedipine tablets produced by nine different manufacturers, validating its practicality for routine pharmaceutical quality control. The developed technique offers a low-cost, high-sensitivity approach for monitoring genotoxic impurities in pharmaceutical formulations, ensuring drug safety and compliance with regulatory standards.