Covalent organic nanospheres as a fiber coating for solid-phase microextraction of genotoxic impurities followed by analysis using gas chromatography–mass spectrometry

Covalent organic nanospheres (CONs) were explored as a fiber coating for solid-phase microextraction of genotoxic impurities (GTIs) from active ingredients (AIs). The CONs were synthesized by an easy solution-phase procedure at 25 °C. The obtained nanospheres exhibited a high specific surface area, good thermostability, high acid and alkali resistance, and favorable crystallinity and porosity. Two types of GTIs—alkyl halides (1-iodooctane, 1-chlorobenzene, 1-bromododecane, 1,2-dichlorobenzene, 1-bromooctane, 1-chlorohexane, and 1,8-dibromooctane) and sulfonate esters (methyl p -toluenesulfonate and ethyl p -toluenesulfonate)—were chosen as target molecules for assessing the performance of the coating. The prepared coating achieved high enhancement factors (EFs: 5097–9799) for the selected GTIs. The strong affinity between CONs and GTIs was tentatively attributed to π–π and hydrophobicity interactions, large surface area of the CONs, and size-matching of the materials. Combined with gas chromatography–mass spectrometry, the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range (0.2–200 ng/g) with a low detection limit (0.04–2.0 ng/g), satisfactory recovery (80.03%–109.5%), and high repeatability (6.20%–14.8%) and reproducibility (6.20%–14.1%). Therefore, the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples. Schematic presentation of fabrication for covalent organic nanospheres via schiff base reaction at room temperature. Then, they were used for ultrasensitive solid-phase microextraction of genotoxic impurities prior to gas chromatography mass spectrometry. • CONs were synthesized and characterized. • CONs were used as sorbents for solid-phase microextraction. • An SPME–GC/MS method was developed for GTI analysis. • This method was successfully applied to GTI analysis of pharmaceutical samples.