Chiral separation of trimetoquinol hydrochloride and related compounds by micellar electrokinetic chromatography using sodium taurodeoxycholate solutions and application to optical purity determination

The chiral separation of trimetoquinol hydrochloride, which is a bronchodilator (Inolin), and three related compounds by micellar electrokinetic chromatography was investigated using a bile salt as a chiral surfactant. Enantiomers of these compounds, except laudanosoline, were successfully separated within 12 min using a separation tube of effective length 500 mm × 0.05 rum i.d. and a 0.05 M sodium taurodeoxycholate solution of pH 7.0. The observed theoretical plate numbers of the peaks were ca. 150000. Chiral recognition was affected by the structure of bile salts, the pH of the buffer solutions used and the structure of the solutes. Of four kinds of bile salts, successful chiral separation was achieved only using sodium taurodeoxycholate solution under neutral conditions. The method was applied to the optical purity determination of trimetoquinol hydrochloride. The effects of surfactant concentrations and some additives to the micellar solution are briefly described.     

Enantioseparation of esbiothrin by cyclodextrin‐modified microemulsion and micellar electrokinetic chromatography

A comparison between chiral cyclodextrin‐modified microemulsion electrokinetic chromatography (CD‐MEEKC) and cyclodextrin‐modified micellar electrokinetic chromatography (CD‐MEKC) for the enantiomeric separation of esbiothrin was carried out. For both methods, the separation conditions were optimized by varying CD types and concentration, running buffer pH and compositions, organic modifiers, and temperature. The optimal CD‐MEEKC conditions were 0.8% n‐heptane, 2.3% SDS, 6.6% n‐butanol, 90.3% 10 mM sodium tetraborate containing 3% (w/v, the ratio of CD mass to microemulsion volume) methyl‐β‐cyclodextrin, pH 10, 25°C. The optimized CD‐MEKC conditions were 3.3% SDS, 96.7% 10 mM sodium tetraborate containing 5% (w/v) β‐CD, pH 10, 25°C. The difference in physicochemical properties of the buffer and CDs resulted in different optimal CD type. The competitive distribution between the microemulsion (or micelle) and chiral CD contributed to the chiral separation. Both methods provided excellent separation (R_s ～? 3) with similar migration time (ca. 15 min). CD‐MEEKC provided higher separation efficiencies (>300000) than CD‐MEKC (>200000). The LODs for CD‐MEEKC and CD‐MEKC were 4.7 μg/mL and 3.2 μg/mL, respectively. The RSDs of migration time and peak area for CD‐MEEKC were slightly higher than for CD‐MEKC. Both the demonstrated CD‐MEEKC and CD‐MEKC methods provided high efficiencies, low LODs, and reproducible enantioseparations of esbiothrin.     

Simultaneous separation of sixteen positional and optical isomers of the tryptophan family by ligand-exchange micellar electrokinetic chromatography

Summary Ligand-exchange micellar electrokinetic chromatography has been used for the simultaneous separation of 16 positional and optical isomers of the tryptophan family. The Cu(II) complex with L-hydroxyproline was used as the chiral selector. Two groups of anionic surfactant, linear alkylbenzenesulfonates (LAS) and straight-chain alkyl sulfates such as sodiumn-decyl sulfate (SDeS), sodium dodecyl sulfate (SDS) and sodiumn-tetradecyl sulfate (STS), were used for simultaneous separation. The best result was obtained by use of SDS. The influence of SDS concentration and of pH on the separation was investigated. The separation behavior in the absence of the Cu(II) complex with L-hydroxyproline was also examined. Use of organic modifiers causes the resolution to decrease. Relationships between the logarithm of the octanol-water partition coefficient (logP _OW) and resolution, and between logP _OW and migration time are discussed.     

Chiral separation with ligand-exchange micellar electrokinetic chromatography using a D-penicillamine-copper(II) ternary complex as chiral selector

D-Penicillamine is demonstrated for the first time as a chiral ligand for the enantioseparation of dansyl amino acids based on ligand-exchange micellar electrokinetic chromatography (LE-MEKC). Copper(II) was used as the central ion in the ternary complex. The effect of surfactant on the resolution was significant. A concentration of 20 mM sodium dodecyl sulfate (SDS) was shown to be necessary for the separation. Other important parameters, such as the concentration ratio of D-penicillamine (D-PEN) to Cu2+, the kind of metal central ion, the type and pH value of buffer, were also investigated. N-Acetyl-D-penicillamine and L-valine (Val), with similar structure to D-penicillamine, were applied as their copper(II) complexes as chiral selector and the chiral recognition mechanism is briefly discussed. Under optimum experimental conditions, i.e., 20 mM NH4OAc, pH 6.5, a 2:1 concentration ratio of D-penicillamine to Cu(II), 4 mM CuSO4 and 8 mM D-penicillamine, the chiral separation of eight pairs of different dansyl amino acid enantiomers was accomplished with resolution ranging from 1.1 to 5.9. When L-PEN was used instead of D-PEN, reversal of the migration order was observed.     

Separation of some chiral flavonoids by microbial cyclosophoraoses and their sulfated derivatives in micellar electrokinetic chromatography

Neutral cyclosophoraoses (Cys) and highly sulfated cyclosophoraoses (HS-Cys) were successfully applied as chiral selectors with SDS for the separation of some chiral flavonoids in MEKC. HS-Cys were synthesized by the chemical modification of a family of neutral Cys isolated from a soil microorganism, Rhizobium meliloti 2011. Chiral catechin was separated with a resolution (R(s)) of 0.754 by neutral Cys and SDS. In the case of isosakuranetin and neohesperidin, resolution (R(s)) values of 1.483 and 1.306 were obtained with HS-Cys and SDS, respectively.     

Dodecyl thioglycopyranoside sulfates: novel sugar-based surfactants for enantiomeric separations by micellar electrokinetic capillary chromatography

Four novel chiral anionic surfactants having carbohydrate hydrophilic heads, sodium n-dodecyl 1-thio-beta-D-glucopyranoside 6-hydrogen sulfate (6-betaGlcD), sodium n-dodecyl 1-thio-beta-L-glucopyranoside 6-hydrogen sulfate (6-betaGlcL), sodium n-dodecyl 1-thio-beta-L-fucopyranoside 3-hydrogen sulfate (3-betaFucL), and sodium n-dodecyl 1-thio-alpha-L-rhamnopyranoside 3-hydrogen sulfate (3-alphaRhaL), were synthesized by selective sulfation of the corresponding thioglycosides. Their CMC determined by fluorescence using pyrene as a probe in water was 1.3-2.7 mM. These surfactants found to be useful as chiral selectors for enantiomeric separation by MEKC. The enantiomeric separation was optimized with respect to pH, buffer concentration, and surfactant concentration. Under the optimized conditions (50 mM phosphate buffer at pH 6.5, 30 mM surfactant, 20 kV), the enantiomeric separations of five dansylated amino acids (Dns-AAs) were achieved within approximately 20 min with the migration order of Val相似文献   

Verification of statistical-overlap theory in micellar electrokinetic chromatography

The limited peak capacity of neutral compounds in micellar electrokinetic chromatography (MEKC) causes peak overlap in a simple 38-compound sample that is predicted by statistical-overlap theory (SOT). The low-concentration sample was prepared in-house from several compound classes to span the entire migration-time range and was resolved partially in a pH=7 phosphate buffer containing 50 mM sodium dodecyl sulfate. Peaks, singlets, doublets, and other multiplets were identified on the basis of known migration times and were counted at 13 voltages spanning 4 – 26 kV. These numbers agreed well with predictions of a simple SOT based on the assumption of an inhomogeneous Poisson distribution of migration times. Because the dispersion theory of MEKC is simple, the standard deviations of single-component peaks were modeled theoretically. As part of a new way to implement SOT, probability distributions of the numbers of peaks, singlets, and so on, were computed by Monte Carlo simulation. These distributions contain all theoretical information on peak multiplicity predictable by SOT and were used to evaluate the agreement between experiment and theory. The peak capacity of MEKC was calculated numerically and substituted into the simplest equations in SOT, affirming that peak overlap arises from limited peak capacity.     

Retention indices in micellar electrokinetic chromatography

The use of retention indices in micellar electrokinetic chromatography (MEKC) is evaluated both from a theoretical and a practical point of view. Fundamental equations for the determination of retention indices in MEKC are described, showing that retention indices are independent of the surfactant concentration. Possibilities as well as limitations of different homologous series as reference standards are described. In addition, the practical application of retention indices for identification, investigation of solute-micelle interactions, characterization and classification of pseudo-stationary phases and determination of solute lipophilicity are discussed.     

Systematic optimization of micellar electrokinetic chromatographic separation of flavonoids

Summary A simple and rapid systematic optimization scheme was described for the micellar electrokinetic chromatographic separation of a group of flavonoids. The scheme employed an interpretative optimization approach to predict the optimum conditions for the separation of a group of flavonoids by micellar electrokinetic chromatography. By performing a set of nine pre-planned experiments conducted over the maximum working range for the system, global optimum separation conditions could be determined. To validate the optimization procedure, additional experiments were performed using the optimum experimental conditions derived from the optimization scheme. The results showed that satisfactory separation of all the peaks could be obtained. In addition, the application of the method in micropreparative micellar electrokinetic chromatography of the flavonoids was demonstrated.     

Comparison of microemulsion electrokinetic chromatography and solvent modified micellar electrokinetic chromatography on rapid separation of heroin, amphetamine and their basic impurities

Microemulsion electrokinetic chromatography (MEEKC) and solvent modified micellar electrokinetic chromatography (MEKC) were investigated with the goal of the rapid separation of complex heroin and amphetamine samples. The rapid simultaneous separation of 17 species of heroin, amphetamine and their basic impurities and adulterants was performed within about 10 min using MEEKC for the first time, whereas solvent modified MEKCs were unable to resolve all the components. The comparisons between MEEKC and solvent modified MEKC proved internal lipophilic organic phase in microemulsions played an important role in improving the separation performance with respect to efficiency. However, the role of internal lipophilic organic phase in MEEKC was disgusted at high concentrations of cosurfactant, and the separations of MEEKC and 1-butanol modified MEKC became similar at high concentrations of 1-butanol. The evaluation of reproducibility, linearity and detection limit of optimized MEEKC method provided good results for all the analytes investigated, thus allowing its application to real controlled drug preparation analysis.     

Cyclodextrin-modified micellar electrokinetic chromatography for separation of norgestrel enantiomers

A simple method for the separation of highly hydrophobic neutral enantiomers by cyclodextrin-modified micellar electrokinetic chro-matography (MEKC) is presented and strongly supported by experiments. The separation depends on the ratio between the concentrations of cyclodextrin (CD) and sodium dodecylsulfate (SDS) micelles and there is an optimum value of the ratio for the separation of the enantiomers of norgestrel and 4-androstene-3,17-dione. At the optimum value of the ratio, obtained by adjusting the absolute concentrations of CD and SDS. The electrophoretic mobility difference between two enantiomers can be maintained nearly constant.     

Chiral ligand exchange micellar electrokinetic chromatography using borate anion as a central ion

Three compounds having 1,2-diol structure (1-phenyl-1,2-ethanediol, 3-phenoxy-1,2-propanediol, and 3-benzyloxy-1,2-propanediol) were enantioseparated by ligand exchange MEKC using (5S)-pinanediol (SPD) as a chiral selector and borate anion as a central ion together with SDS. When (S)-1,2-propanediol, (S)-1,2,4-butanetriol, or (S)-3-tert-butylamino-1,2-propanediol were used as the chiral ligand instead of SPD, these three compounds were not enantioseparated. When borate was replaced with 2-aminoethane-1-sulfonate or N-cyclohexyl-3-aminopropanesulfonate, no chiral separation was achieved. Therefore, the hydrophobic interaction between the chiral selector and the chiral analytes within the transient diastereomeric complex may play an important role in the enantioseparation achieved by the proposed method.     

Separation of anabolic steroids by micellar electrokinetic capillary chromatography

Summary The separation of seven analogous anabolic steroids was studied by micellar electrokinetic capillary chromatography (MECC). The retention order was found to be dependent on polarity. All of these steroids were well separated by the addition of organic modifiers to the separation buffer. Of the organic modifiers tested, 1-propanol gave the best separation, better than methanol or acetonitrile.     

Trace analysis of rapamycin in human blood by micellar electrokinetic chromatography

A capillary electrophoretic method with UV detection at 278 nm has been developed for analysis of the immunosuppressant rapamycin (sirolimus) in human blood at low microgram per liter levels. Separation has been achieved in an acidic carrier electrolyte containing sodium dodecylsulfate and 30% (v/v) acetonitrile. For sample clean-up and preconcentration, an off-line solid-phase extraction step using a silica-based reversed-phase material and an on-capillary focussing technique were employed. The latter allows the injection of increased sample volumes without excessive band broadening. Although this new method is less sensitive than existing liquid chromatographic procedures combined with mass spectrometry, it is fully suited to routine analysis of rapamycin in blood from patients treated with this drug. Last but not least the low costs make it an attractive alternative to established methods.     

混合胶束电动毛细管色谱法分离测定妈富隆片剂中的炔雌醇含量

胆汁酸钠（SC）－十二烷基硫酸钠（SDS）混合胶束电动毛细管色谱法分离测定妈富隆片剂中的炔雌醇，分离缓冲液为SC（55mmol/L)-SDS(15mmol/L)-Tris磷酸（50mmol/L)(pH8.05),分离电压20kV，温度20℃,75μm（i.d)*57.5酮为内标，炔雌醇质量浓度在75．15－901．8μg/mL之间呈良好的线性关系，加样回收率96．4％－104．5％，RSD为3．6％－4．9％（n=3),可用于复方制剂中炔雌醇的含量测定。     

Using micellar electrokinetic chromatography for the highly efficient preconcentration and separation of gold nanoparticles

In this paper, we report the use of micellar electrokinetic chromatography (MEKC) for the highly efficient preconcentration and separation of gold nanoparticles (Au NPs). We used the reversed electrode polarity stacking mode (REPSM) of the MEKC system for the on-line enhancement and separation of the Au NPs. Several parameters had dramatic effects on the systems’ performance, including the concentration of sodium dodecylsulfate (SDS) surfactant, the presence of salts in the NP solution, the pH of the running electrolyte, and the temperature of the capillary. Under the optimized conditions [buffer: SDS (70 mM) and 3-cyclohexylamino-1-propanesulfonic acid (CAPS; 10 mM) at pH 10.0; applied voltage: 20 kV; operating temperature: 25 °C; additive: sodium dihydrogenphosphate (NaH₂PO₄, 10 mM); REPSM strategy for sample preconcentration], the number of theoretical plates for the 5.3- and 40.1-nm-diameter Au NPs were 3000 and (an ultrahigh) 2.1 × 10⁶, respectively; in addition, the detection sensitivities toward the Au NPs were enhanced ca. 20- and 380-fold, respectively, relative to those obtained using standard MEKC analysis conditions. Furthermore, monitoring the electropherograms using diode-array detection allowed us to identify and characterize the sizes of the separated NPs from their UV–vis spectra. Our findings suggest that MEKC is a highly efficient tool for both the preconcentration and separation of NPs.     

Pesticide analysis by micellar electrokinetic capillary chromatography

On-capillary sample concentration using sample stacking for the improvement of detection limits for various pesticides separated by micellar electrokinetic capillary chromatography was examined. The dependence of the stacking on different parameters was investigated. An approximately 30-fold preconcentration was achieved by applying sample stacking. Employing a two-step enrichment process (solid-phase extraction combined with sample stacking), detection limits were improved and the sample volume for SPE was reduced. In addition, the total time for the analysis was considerably reduced. Detection limits were between 0.01 and 0.1 ng/ml under these enrichment conditions.