Enantioseparation and molecular modeling study of eight psychoactive drugs on a coated polysaccharide-based chiral stationary phase.

The enantioseparation of eight psychoactive drugs has been firstly performed on a coated cellulose-based chiral stationary phase (Chiralcel OJ-H). To obtain optimum separation conditions, the influences of alcohol modifiers and basic/acidic additives have been studied. As a result, except for the partial separation of oxybutynin enantiomers, the other seven drug enantiomers including mirtazapine, sulpiride, promethazine, citalopram, oxazepam, donepezil, and cyamemazine have been completely separated. Additionally, for gaining a better insight into the chiral recognition mechanisms, molecular docking was carried out using the Autodock software. Herein, binding energy and conformations of the chiral stationary phase complexes were provided, and it was found that the distinction in enantiomeric conformation determined the number and strength of intermolecular interactions between analytes and chiral stationary phase which resulted in the difference in binding energies of two enantiomers, and ultimately led to the different migration. These modeling results were in accordance with the observed enantioseparation results in high performance liquid chromatography experiments. At last, chiral separation mechanisms have been discussed in detail, and it has been confirmed that hydrogen bond, π-π, hydrophobic interactions, and some special interactions synergistically contributed to the enantioseparation of psychoactive drugs. This article is protected by copyright. All rights reserved.

Hydroxypropyl ß-cyclodextrin nanohybrid monoliths for use in capillary electrochromatography with UV detection: application to the enantiomeric separation of adrenergic drugs, anticholinergic drugs, antidepressants, azoles, and antihistamine.

Two kinds of hydroxypropyl ß-cyclodextrin nanohybrid monoliths were synthesized and applied in capillary electrochromatography with UV detection. One column was fabricated by concurrently using glycidyl methacrylate-bonded hydroxypropyl ß-cyclodextrin (GMA-HP-ß-CD), sodium 3-mercaptopropanesulphonate, and alkoxysilanes in the "one-pot" process. The other was prepared by free radical polymerization of GMA-HP-ß-CD, vinylmethylcyclosiloxane, ethylene dimethacrylate, and 2-acrylamido-2-methyl propane sulfonic acid. Compared to the former hybrid monolith, the latter one displayed improved enantiomeric separation. For ten adrenergic drugs, six anticholinergic drugs, two antidepressants, six azoles, and one antihistamine enantiomeric separation was obtained on the monolith synthesized by free radical polymerization. Twelve out of twenty-five drugs were baseline-separated. Especially, anisodamine with two chiral centers was successfully separated with resolution values of 3.06, 2.11, and 2.17. The nanohybrid monoliths were characterized by optical microscopy, scanning electron microscopy, FT-IR, nitrogen adsorption analysis, and thermogravimetric analysis. Relative standard deviation values less than 5% were obtained through run-to-run, day-to-day, and column-to-column investigations (n = 3). Graphical abstract Schematic representation of two kinds of hydroxypropyl ß-cyclodextrin nanohybrid monoliths based on "one-pot" approach (route I) and free radical polymerization approach (route II), respectively.

Separation and quantitation of notopterol enantiomers in notopterygii rhizoma et radix using solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.

In this study, a specific, sensitive, and reliable high performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantitative determination of notopterol enantiomers in Notopterygii Rhizoma et Radix. Solid-phase extraction was used for the extraction of notopterol enantiomers from Notopterygii Rhizoma et Radix. Enantiomeric separation of notopterol was achieved on a Chiralpak IA column with the mobile phase consisting of acetonitrile-water (50:50, v/v) at a flow rate of 0.6 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source in the positive ionization and multiple reaction monitoring mode. The lower limit of quantification and lower limit of detection were 0.09 and 0.04 mg/g for each enantiomer in NRR samples. And each enantiomer showed good linearity (R2≥0.999) in the range of 0.09-9.55 mg/g. The precision, repeatability, and stability were all within satisfaction. The average recoveries of (-)-notopterol and (+)-notopterol were demonstrated to be 99.3 % and 101.1 %, respectively, with the relative standard deviations less than 5.0 %. Finally, the validated method was successfully applied to the quantification of notopterol enantiomers in Notopterygii Rhizoma et Radix from different sources.

Preparation of a hydroxypropyl-ß-cyclodextrin functionalized monolithic column by one-pot sequential reaction and its application for capillary electrochromatographic enantiomer separation.

In this study, a hydroxypropyl-ß-cyclodextrin (HP-ß-CD) functionalized monolithic capillary column was prepared by one-pot sequential reaction for the first time. The preparation of the HP-ß-CD functionalized monolithic column involves two sequential reactions in one pot: (1) the ring opening reaction between HP-ß-CD and glycidyl methacrylate (GMA) catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); (2) the copolymerization of GMA-HP-ß-CD, ethylene dimethacrylate (EDMA) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS). A series of monolithic columns were successfully prepared by varying the temperature of the ring opening reaction or several copolymerization parameters (the type and composition of porogenic solvents, ratio of GMA-HP-ß-CD to EDMA and polymerization temperature). Then, the morphologies and structures of the resulting monolithic stationary phases were characterized by optical microscopy, scanning electron microscopy (SEM) and nitrogen adsorption analysis. Raman spectroscopy clearly indicated the successful bonding of HP-ß-CD onto the monolith. When the prepared chiral stationary phase (CSP) was applied for the separation of a set of racemic compounds by capillary electrochromatography (CEC), including racemic anticholinergic drugs, ß-adrenergic drugs, meptazinol and its intermediates, satisfactory separation selectivities were obtained. Additionally, the column also showed excellent separation abilities towards four flavanone glycosides epimers. Furthermore, the prepared monolithic columns exhibited satisfactory stability and reproducibilities of retention time, resolution and column efficiency. These results demonstrated the potential and usefulness of the developed one-pot sequential strategy in the preparation of other derivatized CD functionalized monolithic columns.