Enantioseparation of chiral ß-blockers using polynorepinephrine-coated nanoparticles and chiral capillary electrophoresis.

A method of combining magnetic solid-phase separation (MSPE) and chiral capillary electrophoresis (CE) is developed for enantioseparation of trace amounts of ß-blockers. Polynorepinephrine-functionalized magnetic nanoparticles (polyNE-MNPs) are synthesized and applied to simultaneously extract three ß-blockers (carteolol, metoprolol, and betaxolol). The prepared polyNE-MNPs are spherical with a diameter of 198 ± 17 nm and the thickness of the polyNE coating is about 14 nm. PolyNE possesses abundant catechol hydroxyl and secondary amine groups, endowing the MNPs with excellent hydrophilicity. Under the optimum conditions, the extraction efficiencies of polyNE-MNPs for ß-blockers are in the range of 89.6 to 100%, with relative standard deviations (RSDs) below 3.5%. The extraction process can be finished in 4 min. Field-enhanced sample injection (FESI) in chiral CE is constructed to further enhance the sensitivities of ß-blocker enantiomers. The limits of detection for ß-blocker enantiomers by the FESI-CE with polyNE-MNPs are in the range of 0.401 to 1.59 ng mL-1. The practicability of this method in real samples is evaluated by analysis of human urine samples. The recoveries for each enantiomer of ß-blockers in the real samples range from 89.5 to 92.8%, with RSDs ranging from 0.37 to 5.9%. The whole detection process can be finished in less than 0.5 h. The method demonstrates its great potential in the pharmacokinetic and pharmacodynamic studies of chiral drugs in humans. Graphical abstract ᅟ.

A facile and efficient single-step approach for the fabrication of vancomycin functionalized polymer-based monolith as chiral stationary phase for nano-liquid chromatography.

A facile single-step preparation strategy for fabricating vancomycin functionalized organic polymer-based monolith within 100µm fused-silica capillary was developed. The synthetic chiral functional monomer, i.e 2-isocyanatoethyl methacrylate (ICNEML) derivative of vancomycin, was co-polymerized with the cross-linker ethylene dimethacrylate (EDMA) in the presence of methanol and dimethyl sulfoxide as the selected porogens. The co-polymerization conditions were systematically optimized in order to obtain satisfactory column performance. Adequate permeability, stability and column morphology were observed for the optimized poly(ICNEML-vancomycin-co-EDMA) monolith. A series of chiral drugs were evaluated on the monolith in either polar organic-phase or reversed-phase modes. After the optimization of separation conditions, baseline or partial enantioseparation were obtained for series of drugs including thalidomide, colchicine, carteolol, salbutamol, clenbuterol and several other ß-blockers. The proposed single-step approach not only resulted in a vancomycin functionalized organic polymer-based monolith with acceptable performance, but also significantly simplified the preparation procedure by reducing time and labor.

Extraction and preconcentration of beta-blockers in human urine for analysis with high performance liquid chromatography by means of carrier-mediated liquid phase microextraction.

A novel method was developed for the analysis of four beta-blockers, namely sotalol, carteolol, bisoprolol, and propranolol, in human urine by coupling carrier-mediated liquid phase microextraction (CM-LPME) to high performance liquid chromatography (HPLC). By adding an appropriate carrier in organic phase, simultaneous extraction and enrichment of hydrophilic (sotalol, carteolol, and bisoprolol) and hydrophobic (propranolol) drugs were achieved. High enrichment factors were obtained by optimizing the compositions of the organic phase, the acceptor solution, the donor solution, the stirring rate, and the extraction time. The linear ranges were from 0.05 to 10.0 mg L(-1) for sotalol and carteolol, and from 0.05 to 8.0 mg L(-1) for bisoprolol and propranolol. The limits of detection (S/N=3) were 0.01 mg L(-1) for sotalol, carteolol, and bisoprolol, and 0.005 mg L(-1) for propranolol. The relative standard deviations were lower than 6%. The developed method exhibited high analyte preconcentration and excellent sample clean-up effects with little solvent consumption and was found to be sensitive and suitable for simultaneous determination of the above four drugs spiked in human urine. Furthermore, the successful analysis of propranolol in real urine specimens revealed that the determination of beta-blockers in human urine is feasible using the present method.

Nonaqueous capillary electrophoresis: application possibilities and suitability of various solvents for the separation of basic analytes.

Eleven organic solvents were tested for their suitability in the use of capillary electrophoresis (CE). In all cases, 25 mM ammonium acetate and 1 M acetic acid were used as electrolytes. Three basic therapeutical agents, propranolol, carteolol and imipramine, were used as analytes. Four solvents (2-propanol, ethylene glycol, propylene glycol, dichloromethane) were not suitable for use with CE under our conditions. Depending on the other solvents used, the analytes showed very different behavior. We observed that the epsilon/eta quotient alone is not sufficient for a characterization of the solvents. Further investigations with all the solvents as 1:1 mixtures with methanol were carried out. As a result some principal changes occurred compared to the pure solvents. Working with mixtures of different solvents proved to be advantageous because of the possibility to influence properties like high viscosity or low ionizing abilities by the addition of a suitable second solvent.