Hierarchically porous hyper-crosslinked polymer-coated SPME fibers for enrichment and sensitive detection of N-nitrosamine genotoxic impurities in pharmaceutical products.

N-Nitrosamine genotoxic impurities are the most closely monitored pharmaceutical contaminants because of their potent carcinogenicity and stringent regulatory limits. In this work, a novel hyper-crosslinked polymer (HCP)-based analytical method was developed for the highly sensitive determination of trace N-nitrosamine impurities in sartan pharmaceuticals. A hydrophilic HCP with high specific surface area, hierarchical porous architecture, and excellent thermal stability was synthesized via a one-step Friedel-Crafts alkylation reaction using 2,5-dibromonitrobenzene as the functional monomer and 1,4-bis(chloromethyl)benzene as the crosslinker. When coupled with gas chromatography-mass spectrometry (GC-MS), the HCP-coated fiber enabled efficient extraction of trace nitrosamines, resulting in a highly sensitive analytical method for complex pharmaceutical matrices. Under the optimized conditions, excellent linearity was achieved over the concentration range of 5-1000 ng g-1, with correlation coefficients (r) ≥ 0.9994. The method provided low limits of detection of 0.8-1.0 ng g-1 and high enrichment factors ranging from 351 to 2775. Satisfactory recoveries of 90.8-108.6% with relative standard deviations (RSDs) ≤ 10.4% demonstrated the accuracy and reproducibility of the proposed method. The practical applicability of the method was further validated through the successful determination of N-nitrosamine impurities in nine commercially available losartan potassium tablet products. The proposed HCP-SPME-GC-MS strategy provides a cost-effective, sensitive, and robust approach for the monitoring of trace nitrosamine genotoxic impurities in pharmaceutical products.