A novel determination method of quaternary ammonium oxime reactivators and their blood–brain barrier permeability evaluation by surface‐enhanced Raman spectrometry

Abstract The quaternary ammonium oxime reactivators are a class of important reactivators for nerve agents poisoning, and their sensitive and specific analysis in biomedical samples meets many challenges due to their highly polar properties. In present paper, a novel determination method based on surface‐enhanced Raman spectrometry (SERS) was developed for series of quaternary ammonium oxime reactivators. The self‐cleaning effect of iodine anion on the surface of porous shell‐insulated nanoparticles and the electrostatic adsorption effect were proved to be effective to remove the strong interference of protein and other coexisting substances and significantly improve the response intensity and fingerprint feature of Raman peaks. The analysis of five important quaternary ammonium oxime reactivators (PAM‐Cl, TMB‐4, MMB‐4, HI‐6, LüH6) was achieved in biomedical samples, which had the merit of simple sample pretreatment, rapid speed, high sensitivity, and fingerprint peak characteristics. The detection limits reached values of as low as 0.5 ng·mL −1 for dipyridyl quaternary ammonium oxime reactivators. The method has been successfully used for blood concentration monitoring in vivo and evaluation of the liposomes drug delivery ability to penetrate the blood–brain barrier in mice.