Covalent organic nanospheres as a fiber coating for solid-phase microextraction of genotoxic impurities followed by analysis using GC-MS

Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solutionphase procedure at 25℃.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 ptoluenesulfonate),were chosen as target molecules for assessing the performance of the coating.The prepared coating achieved high enhancement factors(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(GC-MS),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.

Simultaneous and Trace Level Quantification of Five Potential Genotoxic Impurities in Ranolazine Active Pharmaceutical Ingredient Using LC-MS/MS

Highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of five potential genotoxic impurities in ranolazine active pharmaceutical ingredient. Chromatographic separation achieved using Poroshell C18 PFP 150 × 3.0 mm 2.7 μ column and 0.1% formic acid in water as Mobile phase A and 0.1% formic acid in methanol as mobile phase B using gradient elution and a flow rate of 0.4 ml/min with a run time of 18 minutes. Mass spectrometric conditions were optimized using electrospray ionization in positive mode. Method shows excellent linearity from 0.05 - 5.0 ppm of the ranolazine test concentration for all the five impurities. The correlation coefficient was observed greater than 0.99. Satisfactory recoveries were observed for all the five impurities within the range of 102.9% - 112.3%. Method has been validated as per ICH recommended guidelines with a LOQ of 0.15 ppm achieved. The developed method was able to quantify all the five impurities at a concentration level of 1 ng/ml (0.5 ppm with respect to 2 mg/ml ranolazine).