Restricted access magnetic core-mesoporous shell microspheres with C8-modified interior pore-walls for the determination of diazepam in rat plasma by LC-MS

In this study, a novel enrichment technique based on magnetic core-mesoporous shell microspheres with C8-modified interior pore-walls (C8-Fe3O4@mSiO2) was successfully developed for the determination of diazepam in rat plasma by LC-MS. Due to the unique properties of the synthesized C8-Fe3O4@mSiO2 microspheres (C8-modified magnetic mesoporous microsphere), small drug molecules like diazepam can enter the mesopore channels and be efficiently absorbed through hydrophobic interaction by interior C8-groups (Octyl functional groups). Large molecules like proteins are excluded from the mesopore channels as a result of size exclusion effect, leading to direct extraction of drug molecules from protein-rich biosmaples such as plasma without any other pretreatment procedure. Moreover, diazepam adsorbed C8-Fe3O4@mSiO2 microspheres could be simply and rapidly isolated through placing a magnet on the bottom of container, and then diazepam could be easily eluted from C8-Fe3O4@mSiO2 microspheres for further LC-MS analysis. Extraction conditions such as amounts of C8-Fe3O4@mSiO2 microspheres added, adsorption time, elution solvent and elution time were investigated. Method validations including linear range, the limit of detection, precision, and recovery were also studied. The results indicated that the proposed method based on C8-Fe3O4@mSiO2 microspheres was simple and accurate for the analysis of diazepam in the rat plasma. And it will provide new ideas for analyzing plasma concentration and pharmacokinetics of similar drugs. ► An enrichment technique based on C8-Fe3O4@mSiO2 microspheres was developed. ► Mesopores on the surface of the microspheres exclude proteins from the sample. ► The C8 groups modified on the inner walls extract drug molecules from the sample. ► The strong magnetic behavior of the microspheres ensure a fast and easy separation.