Enantiomeric analysis of rivastigmine in pharmaceuticals by cyclodextrin-modified capillary zone electrophoresis

Chiral separation method development is usually very time-consuming due to the diversity in chemical structures of pharmaceutical drug substances as well as the suitable separation conditions and the problem to choose the appropriate chiral selector. This paper shows capillary zone electrophoresis (CZE) which was developed for chiral separation of a basic compound - rivastigmine (RIV) using 30 cm × 50 μm i.d. polyacrylamide (PAA)-coated fused-silica capillary (effective length 20 cm), amine-modified phosphate buffer of pH 2.5 and sulfated-β-CD (S-β-CD) as chiral selector. Other selected native or derivatized cyclodextrins (CDs) were also tested: β-CD (5, 30 mM), carboxymethyl-β-CD (5, 30 mM), dimethyl-β-CD (15 mM), hydroxypropyl-β-CD (5, 30 mM), hydroxypropyl-α-CD (5, 30 mM) and hydroxypropyl-γ-CD (5, 30 mM). Complete enantiomeric separation of RIV was achieved at 20 kV, 18 °C and detection at 200 nm within 8 min with R.S.D. for the absolute migration time reproducibility of less than 2.1%. Rectilinear calibration range was 5.0-500.0 μM of each enantiomer (r = 0.9994-0.9995). The CZE method proposed was used for the control of chiral purity of pharmaceutically active S-RIV and for the analysis of Exelon caps preparation.     

Method development and validation for the separation and determination of omeprazole enantiomers in pharmaceutical preparations by capillary electrophoresis

A new capillary zone electrophoresis (CZE) method for the separation of omeprazole enantiomers has been developed. Methyl-β-cyclodextrin (methyl-β-CD) was chosen as the chiral selector, and several parameters, such as cyclodextrin structure and concentration, buffer concentration, pH, and capillary temperature were investigated in order to optimize separation and run times. Analysis times, shorter than 8 min were found using a background electrolyte solution consisting of 40 mM phosphate buffer adjusted to pH 2.2, 30 mM β-cyclodextrin and 5 mM sodium disulphide, hydrodynamic injection, and 15 kV separation voltage. Detection limits were evaluated on the basis of baseline noise and were established 0.31 mg/l for the omeprazole enantiomers. The proposed method was applied to five pharmaceutical preparations with recoveries between 84 and 104% of the labeled contents.     

Enantioseparation of β-substituted tryptophan analogues with modified cyclodextrins by capillary zone electrophoresis

Direct capillary zone electrophoretic methods were developed for the separation of the enantiomers of unnatural β-substituted tryptophan analogues such as erythro- and threo-β-methyl-, β-2-propyl-, β-3-pentyl-, β-phenyl- and β-2,5-dimethoxyphenyltryptophan. Cyclodextrins (CDs) were chosen as chiral selectors because of their favorable properties (stability, commercial availability, low cost, UV transparency, inertness, etc.). Capillary zone electrophoresis was carried out using sulfopropylated-α-CD (SP2-α-CD), sulfopropylated-β-CD (SP2-β-CD) both with a degree of substitution of 2 moles/mole cyclodextrin, and sulfopropylated-β-CD (SP4-β-CD) with a degree of substitution of 4 moles/mole β-cyclodextrin. With this technique all compounds investigated are baseline resolved using different background electrolytes and chiral additives. The elution sequence was determined in all cases.     

Determination of aminoglutethimide enantiomers in pharmaceutical formulations by capillary electrophoresis using methylated-β-cyclodextrin as a chiral selector and computational calculation for their respective inclusion complexes

A capillary electrophoretic method for the separation of the aminoglutethimide (AGT) enantiomers using methylated-β-cyclodextrin (M-β-CD) as chiral selector is described. Several parameters affecting the separation were studied, including the type and concentration of chiral selector, buffer pH, voltage and temperature. Good chiral separation of the racemic mixture was achieved in less than 9 min with resolution factor Rs = 2.1, using a fused-silica capillary and a background electrolyte (BGE) of tris-phosphate buffer solution (50 mmol L⁻¹, pH 3.0) containing 30 mg mL⁻¹ of M-β-CD. The separation was carried out in normal polarity mode at 25 °C, 16 kV and using hydrostatic injection. Acceptable validation criteria for selectivity, linearity, precision, and accuracy/recovery were included. The proposed method was successfully applied to the assay of AGT enantiomers in pharmaceutical formulations. The computational calculations for the inclusion complexes of the R- and S-AGT-M-β-CD rationalized the reasons for the different migration times between the AGT enantiomers.     

A novel capillary electrophoresis method for the determination of d-serine in neural samples

A capillary electrophoresis method has been developed for the determination of d-serine in neural samples. d/l-serine was tagged with naphthalene-2,3-dicarboxaldehyde (CBI-d/l-Ser), and the separation of CBI-d/l-Ser enantiomer was achieved by using a dual chiral selector system consisting of β-cyclodextrin (β-CD) and chiral micelles formed by sodium deoxycholate (SDC). No resolution was observed when either β-CD or SDC was used alone. Moreover, the combined use of β-CD with achiral micelles of sodium dodecylsulfate (SDS) exhibited no resolving effect. With laser induced fluorescence detection, the limit of detection was 3.0 × 10⁻⁸ M Ser. Under the separation conditions selected, no other amino acids co-eluted with l-/d-Ser enantiomers. Using the present method, d-Ser level in Aplysia ganglia homogenates was found to vary significantly from animal to animal. Interestingly, d-Ser was not detected in single neurons isolated from Aplysia ganglia.     

Analysis of amino acids and biogenic amines in breast cancer cells by capillary electrophoresis using polymer solutions containing sodium dodecyl sulfate

We describe simultaneous analysis of naphthalene-2,3-dicarboxaldehyde (NDA)-amino acid and NDA-biogenic amine derivatives by CE in conjunction with light-emitting diode-induced fluorescence detection using poly(ethylene oxide) (PEO) solutions containing sodium dodecyl sulfate (SDS). After sample injection, via EOF 0.1% PEO prepared in 100 mM TB solution (pH 9.0) containing 30 mM SDS entered a capillary filled with 0.5 M TB solution (pH 10.2) containing 40 mM SDS. Under this condition, 14 NDA-amino acid and NDA-amine derivatives were separated within 16 min, with high efficiency ((1.0–3.2) × 10⁵ theoretical plates) and sensitivity (LODs at S/N = 3 ranging from 2.06 to 19.17 nM). In the presence of SDS and PEO, analytes adsorption on the capillary wall was suppressed, leading to high efficiency and reproducibility. The intraday analysis RSD values (n = 3) of the mobilities for the analytes are less than 0.52%. We have validated the practicality of this approach by quantitative determination of 9 amino acids in breast cancer cells (MCF-7) and 10 amino acids in normal epithelial cells (H184B5F5/M10). The concentrations of Tau and Gln in the MCF-7 cells were different than those in the H184B5F5/M10 cells, respectively. Our results show the potential of this approach for cancer study.     

Enantioseparation of dansyl amino acids and dipeptides by chiral ligand exchange capillary electrophoresis based on Zn(II)-l-hydroxyproline complexes coordinating with γ-cyclodextrins

A chiral ligand exchange capillary electrophoresis (CLE-CE) method using Zn(II) as the central ion and l-4-hydroxyproline as the chiral ligand coordinating with γ-cyclodextrin (γ-CD) was developed for the enantioseparation of amino acids (AAs) and dipeptides. The effects of various separation parameters, including the pH of the running buffer, the ratio of Zn(II) to l-4-hydroxyproline, the concentration of complexes and cyclodextrins (CDs) were systematically investigated. After optimization, it has been found that eight pairs of labeled AAs and six pairs of labeled dipeptides could be baseline-separated with a running electrolyte of 100.0 mM boric acid, 5.0 mM ammonium acetate, 3.0 mM Zn(II), 6.0 mM l-hydroxyproline and 4.0 mM γ-CD at pH 8.2. The quantitation of AAs and dipeptides was conducted and good linearity (r² ≥ 0.997) and favorable repeatability (RSD ≤ 3.6%) were obtained. Furthermore, the proposed method was applied in determining the enantiomeric purity of AAs and dipeptides. Meanwhile, the possible enantiorecognition mechanism based on the synergistic effect of chiral metal complexes and γ-CD was explored and discussed briefly.     

Preparation and characterization of hydroxypropyl-β-cyclodextrin inclusion complex of eugenol: differential pulse voltammetry and (1)H-NMR

The objective of present investigation was to improve the solubility of Eugenol by preparing the inclusion complex of Eugenol with hydroxypropyl-β-cyclodextrin (Hp-β-CD) and characterize the prepared complex by using NMR and differential pulse voltammetry (DPV). Phase solubility curve was plotted using Hp-β-CD in ranging from 0-40 mM of Hp-β-CD and found to be linear. Therefore, inclusion complex was prepared in equimolar ratio of Eugenol and Hp-β-CD by lyophilization method. Fourier transform infrared spectroscopy (FT-IR), (1)H-NMR and DPV were performed for Eugenol, Hp-β-CD and prepared inclusion complex of Eugenol. 2D (two dimensional) NMR was also performed for prepared inclusion complex. The proton of phenol moiety of Eugenol experienced a pronounced chemical shift variation in (1)H-NMR. The positive sign of the variation for proton in (1)H-NMR indicated that the proton was located near to an oxygen atom in the Hp-β-CD cavity and its magnitude showed a strong interaction between -OH proton of Eugenol and Hp-β-CD. 2D NMR confirms the interaction between phenolic group and hydrogen atoms of Hp-β-CD. A well defined anodic peak current corresponding to oxidation of Eugenol in non-encapsulated and Hp-β-CD-Eugenol inclusion complex in phosphate buffer (pH 6.8) was obtained at about 0.35 V and 0.40 V, respectively. The positive shift in oxidation potential indicated the formation of complex via hydrophobic interactions. The oxidant power of Eugenol was retained in complex form as indicated by DPV results. Thus, its oxidation dependent pharmacological property such as antimicrobial activity is not affected after complexation with Hp-β-CD. Thus, (1)H-NMR, 2D-NMR and DPV techniques can be used as valuable tools to determine the mechanism of complexation and state of electrochemical active drug in inclusion complex.     

Development and validation of a nonaqueous capillary electrophoretic method for the enantiomeric purity determination of a synthetic intermediate of new 3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans using a single-isomer anionic cyclodextrin derivative and an ionic liquid

The enantiomeric purity determination of a synthetic intermediate of new 3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans, i.e. 4-amino-2,2-dimethyl-6-ethoxycarbonylamino-3,4-dihydro-2H-1-benzopyran, was successfully carried out using an anionic cyclodextrin (CD) derivative combined with a chiral ionic liquid (IL). In order to obtain high resolution and efficiency values, the addition of a chiral IL, i.e. ethylcholine bis(trifluoromethylsulfonyl)imide (EtChol NTf₂), to the background electrolyte containing heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) was found to be essential. A simultaneous increase in separation selectivity and enantioresolution seems to indicate a synergistic effect of HDMS-β-CD and EtChol NTf₂. The best enantioseparation of the key intermediate was achieved using a methanolic solution of 0.75 M formic acid, 10 mM ammonium formate, 1.5 mM HDMS-β-CD and 5 mM EtChol NTf₂. Levamisole was selected as internal standard. The optimized conditions allowed the determination of 0.1% of each enantiomer in the presence of its stereoisomer using the method of standard additions. The NACE method was then fully validated with respect to selectivity, response function, trueness, precision, accuracy, linearity and limits of detection and quantification.     

Hydroxyethylammonium monosubstituted cyclodextrin as chiral selector for capillary electrophoresis

A novel cationic cyclodextrin, mono-6^A-(2-hydroxyethyl-1-ammonium)-6^A-β-cyclodextrin chloride (HEtAMCD) has been successfully synthesized and applied as chiral selector in capillary electrophoresis. The NMR study revealed this chiral selector has three recognition sites: β-CD, ammonium cation and hydroxy group in the sidearm to contribute three corresponding driving forces including inclusion complexation, electrostatic interaction and hydrogen bonding. The effect of buffer pH and HEtAMCD concentration (2.5–10 mM) on enantioselectivity, chiral resolution as well as effective mobility of analytes was investigated. This elegantly designed CD exhibits outstanding enantioselectivities toward the studied hydroxyl acids and ampholytic racemates in CE with the aid of extra hydrogen bonding. Under optimum pH 6.0, chiral resolutions over 5 can be readily obtained for hydroxy acids with CD concentration below 5 mM. The comparison study between HEtAMCD and our earlier reported ammonium CDs indicates the hydroxyethylammonium group of HEtAMCD significantly increased the enantioselective capability.     

On-line concentration and separation of indolamines, catecholamines, and metanephrines in capillary electrophoresis using high concentration of poly(diallyldimethylammonium chloride)

This paper tackles a simple and efficient method for the simultaneous separation and stacking of neurotransmitters in capillary electrophoresis with UV detection. By using poly(diallyldimethylammonium chloride) (PDDAC) as a buffer additive, the high and reversed EOF are observed. Moreover, the mobility of indolamines and catecholamines decreases as the PDDAC concentration increases. Based on the difference in mobility in the presence and absence of PDDAC, the analytes were simply stacked between the boundary of the sample zone and the background electrolyte containing PDDAC. The separation of 14 analytes including indolamines, catecholamines, and metanephrines was accomplished within 33 min under optimal conditions (1.2% PDDAC and 5 mM formic acid at pH 4.0), and the values of relative standard deviation of their migration time were less than 3.1%. By applying stacking methods for fourteen analytes, we observed: (a) the sample injection volume of sample is up to 216 nL, (b) the limits of detection at signal-to-noise of 3 range from 15.4 to 122.1 nM, and (c) the sensitivity enhancements, compared to normal injection (12 nL), range from 110- to 220-fold. Under the optimal stacking conditions, the present method has been applied to analyze of vanillomandelic acid, 5-hydroxyindole-3-acetic acid, dopamine, tryptamine, and 3-indoxyl sulfate in urine samples.     

Enantioselective analysis of ofloxacin and ornidazole in pharmaceutical formulations by capillary electrophoresis using single chiral selector and computational calculation of their inclusion complexes

A capillary electrophoretic method for the separation of the enantiomers of both ofloxacin and ornidazole is described. Several parameters affecting the separation were studied, including the type and concentration of chiral selector, buffer pH, voltage and temperature. Good chiral separation of the racemic mixtures was achieved in less than 16 min with resolution factors Rs = 5.45 and 6.28 for ofloxacin and ornidazole enantiomers, respectively. Separation was conducted using a bare fused-silica capillary and a background electrolyte (BGE) of 50 mM H₃PO₄-1 M tris solution; pH 1.85; containing 30 mg mL⁻¹ of sulfated-β-cyclodextrin (S-β-CD). The separation was carried out in reversed polarity mode at 25 °C, 18 kV, detection wavelength at 230 nm and using hydrodynamic injection for 15 s. Acceptable validation criteria for selectivity, linearity, precision, and accuracy were studied. The limits of detection (LOD) and limits of quantitation (LOQ) of the enantiomers (ofloxacin enantiomer 1 (OF-E1), ofloxacin enantiomer 2 (OF-E2), ornidazole enantiomer 1 (OR-E1) and ornidazole enantiomer 2 (OR-E2)) were (0.52, 0.46, 0.54, 0.89) and (1.59, 1.40, 3.07, 2.70) μg mL⁻¹, respectively. The proposed method was successfully applied to the assay of enantiomers of both ofloxacin and ornidazole in pharmaceutical formulations. The computational calculations for the enantiomeric inclusion complexes rationalized the reasons for the different migration times between the ofloxacin and ornidazole enantiomers.     

Optimisation of a Headspace Solid-Phase Micro- Extraction Procedure for the Determination of 2,4,6-Trichloroanisole and Various Related Compounds in Cork Washing Waste Water by Use of Gas Chromatography-Mass Spectrometry

This paper reports the use of an anionic cyclodextrin, heptakis(2,3-di-O-methyl-6-O-sulfato)-β-cyclodextrin (HDMS-β-CD), for chiral separations of pharmaceutical enantiomers by nonaqueous capillary electrophoresis (NACE). Enantiomer resolution was affected mainly by HDMS-β-CD concentration and the acidity of the background electrolyte (BGE). The effects of capillary length and applied voltage on enantiomer resolution were also investigated. Results showed that in a methanol solution of 20 mM phosphoric acid, 10 mM sodium hydroxide, and 10 mM HDMS-β-CD, seven anticholinergic drugs were separated to baseline but no chiral separation was obtained for three other similar drugs. NACE is suitable for routine, rapid separation of the enantiomers of pharmaceutical compounds.     

Methoxypropylamino β-cyclodextrin clicked AC regioisomer for enantioseparations in capillary electrophoresis

In this work, a novel methoxypropylamino β-cyclodextrin (β-CD) clicked AC regioisomer, 6^A-4-hydroxyethyl-1,2,3-triazolyl-6^C-3-methoxypropylamino β-cyclodextrin (HETz-MPrAMCD), was synthesized via nucleophilic addition and click chemistry. The chiral separation ability of this AC regioisomer cationic CD was evaluated toward 7 ampholytic and 13 acidic racemates by capillary electrophoresis. Dependence of enantioselectivity and resolution on buffer pH (5.5–8.0) and chiral selector concentration (0.5–7.5 mM) was investigated. Enantioselectivities (α ≥ 1.05) could be achieved for most analytes under optimal conditions except dansyl-dl-noreleucine and dansyl-dl-serine. The highest resolutions for 2-chloromandelic acid p-hydroxymandelic acid were 15.6 and 9.7 respectively. The inclusion complexation between HETz-MPrAMCD and each 3-phenyllactic acid enantiomer was also revealed with nuclear magnetic resonance study.     

Separation of chiral primary amino compounds by forming a sandwiched complex in reversed-phase high performance liquid chromatography

Separation of chiral primary amino compounds was efficiently achieved under reversed-phase high performance liquid chromatography (RP-HPLC) conditions using a mixture of non-chiral crown ether (18-crown-6) and dimethyl-β-cyclodextrin (DM-β-CD) in the mobile phase. Under these conditions, the amino group of the chiral compound was protonated in a low pH mobile phase, and then interacted with 18-crown-6 and DM-β-CD to form a sandwiched complex [18-crown-6 + amine + CD]. Enantiomers of the compound in the sandwiched complex were separated with good enantioselectivity. Formation of the sandwiched complex among the chiral compound and additives in the mobile phase is a key step of the chiral separation. Four different chiral amino compounds namely, 1-aminoindan (AI), 1,2,3,4-tetrahydro-1-naphthylamine (THNA), tyrosine (Tyr), and phenylalanine (Phe), were selected to demonstrate the separation using the sandwiched complex mechanism in RP-HPLC.     

Steroselective determination of trihexyphenidyl using carboxylmethyl-β-cyclodextrin by capillary electrophoresis with field-amplified sample stacking

A simple, sensitive and low-cost method using capillary electrophoresis coupled with field-amplified sample stacking (FASS) technique has been developed for enantioselective separation and quantification of trihexyphenidyl (THP) enantiomers in human serum. In this work, three kinds of modified β-cyclodextrin were tested as chiral selectors in CE. Among the CDs studied, THP enantiomers could only be separated by carboxylmethyl-β-cyclodextrin (CM-β-CD). A systematic study of the parameters (CD concentration and pH value in CE buffer, separation voltage and temperature, composition of sample solvent, injection voltage and time) affecting chiral separation and on-line concentration of THP enantiomers were investigated and optimized. The optimum FASS method provided a sensitivity enhancement of about 490-fold compared with usual hydrodynamic injection. Limits of detection for each enantiomer were in the low ng ml^− 1 concentration range (0.92 ng ml^− 1 or 3.06 nM). The quantification of each THP enantiomer in human serum was performed after serum sample extraction. To validate this CE-FASS method, linear regression analysis, intra and inter-day precision and recovery were determined with satisfying results.     

Chiral separation of raltitrexed by cyclodextrin-modified micellar electrokinetic chromatography

A rapid and effective method was developed for the chiral separation of raltitrexed (RD) enantiomers by carboxymethyl-beta-cyclodextrin (CM-β-CD)-modified micellar electrokinetic chromatography (MEKC). Optimization of conditions including the type and concentration of the chiral selector, concentration of sodium dodecyl sulfate (SDS), pH and concentration of the background electrolyte (BGE), capillary temperature, and applied voltage was investigated. The enantiomers of raltitrexed could be separated with satisfactory resolution and linear response by using 75 mM Tris-phosphate at pH 8.0 containing 30 mM SDS and 8 mM CM-β-CD as buffer system. Furthermore, the usefulness of this method was demonstrated in a purity test of a real synthetic drug sample. Figure Chiral separation of raltitrexed by CM-β-CD MEKC was optimized and applied to test the purity of a synthetic drug sample     

Stacking and separation of fluorescent derivatives of amino acids by micellar electrokinetic chromatography in the presence of poly(ethylene oxide)

A new approach for the analysis of large-volume naphthalene-2,3-dicarboxaldehyde (NDA) derivatives of amino acids by micellar electrokinetic chromatography (MEKC) in conjunction with a purple light-emitting diode-induced fluorescence detection is described. In order to optimize resolution, speed, and stacking efficiency, a discontinuous condition is essential for the analysis of NDA-amino acid derivatives. The optimum conditions use 2.0M TB (pH 10.0) buffer containing 40mM sodium dodecyl sulfate (SDS) to fill the capillary, deionized water to dilute samples, and 200mM TB (pH 9.0) containing 10mM SDS to prepare 0.6% poly(ethylene oxide) (PEO). Once high voltage is applied, PEO solution enters the capillary via electroosmotic flow and SDS micelles interact and thus sweep the NDA-amino acid derivatives having smaller electrophoretic mobilities than that of SDS micelles in the sample zone. When the aggregates between SDS micelles and NDA amino acid derivatives enter PEO zone, they are stacked due to decrease in electric field and increases in viscosity. Under the optimum conditions, the concentration and separation of 0.53-microL 13 NDA-amino acid derivatives that are negatively charged has been demonstrated by using a 60-cm capillary, with the efficiencies 0.3-9.0x10(5) theoretical plates and the LODs at signal-to-noise ratio 3 ranging from 0.30 to 2.76nM. When compared to standard injection (30-cm height for 10s), the approach allows the sensitivity enhancements over the range of 50-800 folds for the derivatives. The new approach has been applied to the analysis of a red wine sample, with great linearity of fluorescent intensity against concentrations (R(2)>0.98) and the RSD (three repetitive runs in one day) values of the migration times for the ten identified amino acids less than 2.8%.     

Fast determination of flavonoids in Hippophae rhamnoides and its medicinal preparation by capillary zone electrophoresis using dimethyl-beta-cyclodextrin as modifier

A fast capillary zone electrophoresis (CZE) method, using dimethyl-β-cyclodextrin (DM-β-CD) as modifier, has been developed for the determination of three flavonoids (quercetin (QU), kaempferol (KA) and isorhamnetin (IS)) in the Chinese herbal extract from Hippophae rhamnoides and its medicinal preparation (Sindacon tablet). Optimum separation was achieved with 20 mM borate buffer at pH 10.0 containing 5 mg ml⁻¹ of DM-β-CD. The applied voltage was 15 kV and the capillary temperature was kept constant at 25 °C. Regression equations revealed linear relationships (correlation coefficients: 0.9973, 0.9992 and 0.9996) between the peak area of each compound (QU, KA and IS) and its concentration. The relative standard deviations of migration times and peak areas were <1.53 and 4.14%, respectively. The effects of several CE parameters on the resolution were studied systematically. The contents of three flavonoids in H. rhamnoides were successfully determined with 4.5 min, with satisfactory repeatability and recovery. It was also tested that the possibilities of using this method for the determination of flavonoids in Chinese medicinal preparation.     

Separation of amino acids and amines by capillary electrophoresis using poly(ethylene oxide) solution containing cetyltrimethylammonium bromide

We describe simultaneous analysis of naphthalene-2,3-dicarboxaldehyde (NDA)-amino acid and amine derivatives by capillary electrophoresis in conjunction with light-emitting diode-induced fluorescence (LEDIF) detection using poly(ethylene oxide) (PEO) containing cetyltrimethylammonium bromide (CTAB). In the presence of CTAB and acetonitrile (ACN), adsorption of PEO on the capillary wall is suppressed, leading to generation of a fast and reproducible electroosmotic flow (EOF). In order to optimize separation resolution and speed, 100 mM Tris–borate solution (pH 7.0) containing 20 mM CTAB and 25% ACN was used to fill the capillary and to prepare 1.2% PEO that entered the capillary via EOF. The analysis of 14 NDA-amino acid and -amine derivatives by this approach is rapid (< 4 min), efficient ((0.9–6.4) × 10⁵ theoretical plates), and sensitive (the LODs (S/N = 3) range from 9.5 to 50.5 nM). The RSD values (n = 5) of the migration times and peak heights of the analytes for the intraday analysis are less than 1.5 and 1.2%, respectively. We have validated the practicality of this approach by quantitative determination of 10 amino acids and amines in a beer samples within 4 min.