Separation Of Drug Enantiomers Research Articles

Toward efficient enantioseparation of ibuprofen isomers using chiral BNNTs: Dispersion corrected DFT calculations and DFTB molecular dynamic simulations

The separation of drug enantiomers in pharmaceutical industry is one of great importance since most organic compounds are chiral. In this study, the separation of ibuprofen enantiomers and the interaction between right-handed (R) and left-handed (S) isomers of ibuprofen with the outer surface as well as internal sidewall of a chiral boron nitride nanotube (BNNT(10,5)) was evaluated. The geometry optimizations and total energy calculations were performed with DFT–D3/revPBE-GGA method for various adsorption configurations. Our first-principles findings showed that interaction strength of the incorporated enantiomers into the BNNTs was higher than ones adsorbed onto the outer surface of nanotube. Also, the interaction energy difference between two enantiomers interacting with inside and outside of the BNNT was about 0.63 and 1.25 kcal/mol, respectively. This finding indicated the more ability of outer surface of BNNT in efficient enantioseparation of Ibuprofen isomers rather than inner site. Furthermore, in order to model a realistic system, tight-binding density functional molecular dynamics (DFTB–MD) simulation was performed at room temperature, and the results were consisted with the DFT–D3 findings. The nudged elastic band (NEB) method was also used to evaluate the activation energy barrier for incorporation of ibuprofen into the BNNT cavity. Our molecular simulation findings are reliable to offer beneficial information about the potential application of chiral BNNTs in enantiomer molecules adsorption and separation.

A Novel Two-Step Liquid-Liquid Extraction Procedure Combined with Stationary Phase Immobilized Human Serum Albumin for the Chiral Separation of Cetirizine Enantiomers along with M and P Parabens.

The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage forms, besides the active substance in large amounts there are usually also inactive ingredients such as methyl- and propylparaben. Unfortunately, these compounds can interfere with the analyte, inter alia during chiral separation of the analyte enantiomers. The proposed innovative two-step liquid-liquid extraction procedure allowed for the determination of cetirizine enantiomers (along with M and P parabens) also in liquid dosage forms. The main focus of this study was the chromatographic activity of cetirizine dihydrochloride on the proteinate-based chiral stationary phase. The chromatographic separation of cetirizine enantiomers was performed on an immobilized human serum albumin (HSA) column for the first time. Measurements were performed at a wavelength of 227 nm. Under optimal conditions, baseline separation of two enantiomers was obtained with 1.43 enantioseparation factor (α) and 1.82 resolution (Rs). Finally, the proposed method was successfully applied to the selected pharmaceutical formulations.

Enantiomer separation of drugs by capillary electrophoresis using mixtures of β-cyclodextrin sulfate and neutral cyclodextrins

Enantiomer separation of drugs by capillary electrophoresis using mixtures of β-cyclodextrin sulfate and neutral cyclodextrins

Enantiomer separation of drugs by capillary electrophoresis using mixtures of beta-cyclodextrin sulfate and neutral cyclodextrins.

Direct separation of enantiomers of drugs was investigated by capillary electrophoresis employing mixtures of charged cyclodextrin derivatives (CDs) and electrically neutral CDs (i.e., dual CD system). Among various charged CDs employed, it was found that beta-CD sulfate showed relatively wide enantioselectivity for a wide variety of drugs under acidic conditions. Then separation of enantiomers was performed by employing beta-CD sulfate and the effect of the addition of electrically neutral CDs to the buffers containing beta-CD sulfate was investigated. Through the addition of electrically neutral CDs to the buffers containing the charged CD, resolution of most of the enantiomers was improved, compared with those with the charged CD alone. It was also found that the ring size (alpha, beta, gamma,), the substitution groups and the concentration of the additional electrically neutral CDs affected the enantioselectivity. For example, alpha-CD addition was effective for the separation of enantiomers of chlorpheniramine and hydroxypropyl-beta-CD was effective for the enantiomer separation of trimetoquinol isomer. The application of the method in optical purity testing is also briefly mentioned.

Determination of binding constants and the influence of methanol on the separation of drug enantiomers in cyclodextrin modified capillary electrophoresis

Binding constants of the optical isomers of phenylalkylamine derivatives and (2,6-di-O-methyl)-β-cyclodextrin were determined using electrophoretic mobility data gained from separations performed by capillary electrophoresis, and assuming a simple equilibrium model. Dependence of the optimum separation conditions and parameters on the binding constants were investigated and the influence of methanol was estimated.

Separation of drug enantiomers by capillary electrophoresis: α-cyclodextrin as chiral solvating agent

Enantiomer separation by capillary zone electrophoresis was studied for a set of 59 chiral drugs. With α-cyclodextrin as chiral solvating agent, six enantiomeric pairs could be resolved. Baseline separation was achieved for clidinium bromide, oxomemazine and tetryzoline, whereas ketamine, orphenadrine, tropicamide and others require further optimization. Aliphatic and monocyclic compounds prevail among compounds recognized by α-cyclodextrin. Statistical analysis reveals that a medium degree of migration retardation offers the best chance for successful separation.

Use of a naphthylethylcarbamoylated‐β‐cyclodextrin chiral stationary phase for the separation of drug enantiomers and related compounds by sub‐ and supercritical fluid chromatography

Use of a naphthylethylcarbamoylated‐β‐cyclodextrin chiral stationary phase for the separation of drug enantiomers and related compounds by sub‐ and supercritical fluid chromatography

Direct injection assay of drug enantiomers in serum on ovomucoid-bonded silica materials by liquid chromatography

A high-performance liquid chromatographic (HPLC) method for the determination of drug enantiomers in serum was developed. The method involves direct injection of serum samples on to an ovomucoid-bonded column, which is prepared by bonding of ovomucoid proteins to an aminopropyl-silica gel by the N,N′-disuccinimidyl carbonate activation method and separation of drug enantiomers on the column using a mixture of phosphate buffer and an organic solvent. High recoveries of serum proteins were obtained using eluent pH values of 3, 4, 6 and 7 at phosphate buffer concentrations above 50 m M, whereas the recovery was ca. 70% at an eluent pH of 5. The recovery of each enantiomer of basic and acidic drugs from serum was almost 100%.

Separation of drug enantiomers by HPLC using chiral stationary phases — A selective review

Enormous progress has been made during the past two decades in the resolution of enantiomers by HPLC. A great variety of chiral HPLC-phases have been developed and applied to various classes of substance. Basically this review will focus on the most recent developments in the preparation of chiral phases and on their application to the resolution of racemic drugs.