A Novel Method for Monitoring N-Nitrosamines Impurities Using NH₂-MIL-101(Fe) Mediated Dispersive Micro-Solid Phase...

A highly efficient and convenient method for the simultaneous determination of 12 N-nitrosamines (NAs) has been developed using an amine-functionalized metal-organic framework (NH₂-MIL-101(Fe)) as sorbent for dispersive micro-solid phase extraction (D-μSPE) coupled with LC-MS/MS in biopharmaceuticals. The experimental variables involved in the extraction process (i.e., amount of the sorbent, extraction time, desorption time, ionic strength, desorption solvent and volume) were optimized to achieve the best extraction efficiency of the target analytes. Under the optimum conditions, the method was successfully validated, showing good linearity in the range of 0.5-3.0 μg/L with determination coefficients (R²) higher than 0.990, repeatability (RSD ≤ 10.0%, spiked level at 2.0 μg/L) and precision (RSD ≤ 8.2%). The limit of detection (LOD) and limit of quantitation (LOQ) were in the range of 0.005-0.025 μg/L and 0.010-0.250 μg/L, respectively. Satisfactory recoveries ranging from 82.4 to 116.8% were obtained by spiking standards at three different concentrations (0.5 μg/L, 2.0 μg/L and 3.0 μg/L). Other validation parameters, including specificity, stability, and robustness, met the validation criteria. More importantly, the plausible adsorption mechanism on NH₂-MIL-101(Fe) was proposed by Fourier-transform infrared (FTIR) spectra technique. Finally, this method was successfully applied to detect trace nitrosamines in biopharmaceuticals.