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Cooperative Retention of Nonsteroidal Anti-inflammatory Drugs on Polyamine-Based Mixed-Mode Chromatographic Stationary Phases

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Abstract

The mixed-mode chromatographic behavior of five non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, naproxen, sulindac and diclofenac on three amine-bonded silica stationary phases was investigated. Diethylamine, ethylenediamine, and tetraethylenepentamine are respectively covalently bonded to epoxy-functionalized silica to generate weak anion exchangers with an increased number of amine groups in the ligands. The bond densities of the functional groups on the synthesized stationary phases were established by Fourier-transform infrared spectroscopy and elemental analysis. The separation of five acidic NSAIDs was successfully achieved on these stationary phases using a mobile phase consisting of 20 mM ammonium formate solution (pH 6.7) in 20% methanol. The effects of pH, organic solvent and ionic strength in the mobile phase on solute retention were investigated. By applying the cooperative binding model based on the formation of a closed cyclic binary complex between the solute and the stationary phase ligand, the observed retention factor can be factored into three distinct contributing components, corresponding to reversed-phase retention, ion-exchange retention and cooperative reversed-phase/ion exchange retention mechanism. The results showed that except for the weaker hydrophobic aspirin, the retention of the other four acidic drugs was essentially controlled by a cooperative retention mechanism. The cooperativity factor, which reflects the probability of complex formation, increases with the hydrophobicity of the solute and the number of adjacent amine groups in the ligand. Based on the enhanced separation power of mixed-mode chromatography on polyamine-bonded silica, this method is expected to have significant advantages in simultaneous determination of trace multi-drug residues in environmental samples when coupled with electrospray ionization mass spectrometry.

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Acknowledgements

We thank Prof. Lei Chen from Tianjin University for stimulating discussions.

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  1. School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, China

    Mengrou Dong & Qian-Hong Wan

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  1. Mengrou Dong
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10337_2022_4191_MOESM1_ESM.docx

FTIR spectra of amine bonded silica, and plots showing the effects of pH and organic solvent percentage on solute retention Supplementary file1 (DOCX 568 KB)

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Dong, M., Wan, QH. Cooperative Retention of Nonsteroidal Anti-inflammatory Drugs on Polyamine-Based Mixed-Mode Chromatographic Stationary Phases. Chromatographia 85, 921–929 (2022). https://doi.org/10.1007/s10337-022-04191-7

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