Monomeric and polymeric anionic gemini surfactants and mixed surfactant systems in micellar electrokinetic chromatography. Part II: characterization of chemical selectivity using two linear solvation energy relationship models

Sodium di(undecenyl) tartarate monomer (SDUT), a vesicle-forming amphiphilic compound possessing two hydrophilic carboxylate headgroups and two hydrophobic undecenyl chains, was prepared and polymerized to form a polymeric vesicle (i.e., poly-SDUT). The anionic surfactants of SDUT and poly-SDUT (carboxylate head group) and sodium dodecyl sulfate, SDS (sulfate head groups) as well as mixed surfactant systems (SDS/SDUT, SDS/poly-SDUT, and SDUT/poly-SDUT) were applied as pseudostationary phases in micellar electrokinetic chromatography (MEKC). Two linear solvation energy relationship (LSER) models, i.e., solvatochromic and solvation parameter models, were successfully applied to investigate the effect of the type and composition of pseudostationary phases on the retention mechanism and selectivity in MEKC. The solvatochromic and solvation parameter models were used to help understand the fundamental nature of the solute-pseudostationary phase interactions and to characterize the properties of the pseudostationary phases (e.g., solute size and hydrogen bond-accepting ability for all pseudostationary phases). The solute types were found to have a significant effect on the LSER system coefficients and on the predicted retention factors. Although both LSER models provide the same information, the solvation parameter model is found to provide much better results both statistically and chemically than the solvatochromic model.     

Thermodynamic studies of the interaction of molecular micelles and copolymerized molecular micelles with benzodiazepines and alkyl phenyl ketones using MEKC

In this study, polymers of sodium 10-undecenoyl L-leucinate (SUL) and sodium undecenyl sulfate (SUS) as well as their copolymerized molecular micelles (CoPMMs) were applied in MEKC as pseudostationary phases to separate benzodiazepines and alkyl phenyl ketones. SDS, a common pseudostationary phase used in MEKC, was also used for comparison. The van't Hoff relationship was applied to compute the temperature dependence of the MEKC retention factors of the test solutes to estimate the enthalpy, entropy, and the Gibbs free energy. Nonlinear van't Hoff plots were obtained with the majority of benzodiazepines indicating that the thermodynamic parameters were temperature-dependent in all surfactant systems for these solutes. In contrast, all alkyl phenyl ketones resulted in linear van't Hoff plots.     

Binary mixed micelles of chiral sodium undecenyl leucinate and achiral sodium undecenyl sulfate: I. Characterization and application as pseudostationary phases in micellar electrokinetic chromatography

Sodium 10-undecenyl sulfate (SUS), sodium 10-undecenyl leucinate (SUL) and their five different mixed micelles at varied percent mole ratios were prepared. The critical micelle concentration (CMC), C₂₀, γ_CMC, partial specific volume, methylene group selectivity, mobilities and elution window were determined using a variety of analytical techniques. These surfactant systems were then evaluated as novel pseudostationary phases in micellar electrokinetic chromatography (MEKC). As a commonly used pseudostationary phase in MEKC, sodium dodecyl sulfate (SDS) was also evaluated. The CMC values of SUS and SUL were found to be 26 and 16 mM, respectively, whereas the CMC of mixed surfactants was found to be very similar to that of SUL. The C₂₀ values decreased dramatically as the concentration of SUL is increased in the mixed micelle. An increase in SUL content gradually increased the methylene group selectivity making the binary mixed surfactants more hydrophobic. Linear solvation energy relationships (LSERs) and free energy of transfer studies were also applied to predict the selectivity differences between the surfactant systems. The cohesiveness and the hydrogen bond acidic character of the surfactant systems were found to have the most significant influence on selectivity and MEKC retention. The SUS and SDS showed the strongest while SUL showed the weakest hydrogen bond donating capacity. The basicity, interaction with n and π-electrons of the solute and dipolarity/polarizability were the least significant factors in LSER model for the surfactant systems studied. Free energies of transfer of selected functional groups in each surfactant systems were also calculated and found to be in good agreement with the LSER data.     

New Pseudostationary Phases for Electrokinetic Chromatography: A High-Molecular Surfactant and Proteins

To extend the applicability of electrokinetic chromatography (EKC), two new types of pseudostationary phases have been introduced. A high-molecular surfactant, butyl acrylate/butyl methacrylate/methacrylic acid copolymer (BBMA) is employed as a micellar forming surfactant for miccllar electrokinetic chromatography (MEKC). The critical micelle concentration of BBMA is essentially zero, which means the micellar concentration is constant irrespective of temperature and buffer. Some characteristic features of BBMA as the pseudostationary phase for MEKC is investigated in comparison with conventional ionic surfactants. Ovomucoid and avidin, which are proteins isolated from egg white, have been found to be useful chiral selectors in affinity EKC. A few examples of the separation of enantiomers with these proteins are shown.     

Novel approach to the analysis and use of fullerenes in capillary electrophoresis

The analysis and use of fullerenes in capillary electrophoresis (CE) was investigated. Sodium dodecyl sulfate (SDS) was used to solubilize fullerenes C60, C70, and a mixture of C60 and C70 in water. The behavior of the solutions of the C60- and C70-SDS complexes was examined by CE with on-line UV-Vis diode array detection. This study included the use of a C60-SDS complex as a new method of micellar electrokinetic chromatography (MEKC) for the separation of polycyclic aromatic hydrocarbons (PAHs) using CE with uniwavelength detection. Since SDS micelles act as a pseudostationary phase in which the PAH compounds partition with their hydrophobic interior, the addition of C60 within the micelles enhanced separation of the PAHs. The preliminary results using C60-MEKC with SDS were compared to those obtained with MEKC with SDS. The capillary electrophoretic separations were performed in 10 mM borate-phosphate buffer with 100 mM SDS at pH 9.5.     

Solute-solvent interactions in micellar electrokinetic chromatography: V. Factors that produce peak splitting

The experimental conditions that produce analyte peak splitting in micellar electrokinetic capillary chromatography (MEKC) have been systematically investigated. The system studied was a neutral phosphate buffer and sodium dodecyl sulfate (SDS) micelles as pseudostationary phase. A number of analytes showing a wide variety of hydrophobicity values and several organic solvents as sample diluents have been tested. Peak splitting phenomena are mainly due to the presence of organic solvent in the sample solution. They increase with the hydrophobicity of the analyte and decrease with the increase of the surfactant concentration. When hydrophobic compounds are analyzed the suggested ways to avoid split peaks are: (i) the use of 1-propanol or 1-butanol as sample diluent instead of methanol or acetonitrile or (ii) the use of high concentration of surfactant in the separating solution when the analyte must be dissolved in pure methanol or acetonitrile.     

Copolymerized polymeric surfactants: characterization and application in micellar electrokinetic chromatography

An achiral monomeric surfactant (sodium 10-undecenyl sulfate, SUS) and a chiral surfactant (sodium 10-undecenoyl L-leucinate, SUL) were synthesized and polymerized individually to form poly-SUS and poly-SUL. These surfactants were then copolymerized at various molar ratios to produce a variety of copolymerized surfactants (CoPSs), possessing both achiral (sulfate) and chiral (leucinate) head groups. The CoPSs, poly-SUS, poly-SUL, and sodium dodecyl sulfate were characterized using several analytical techniques. The aggregation numbers of the polymeric surfactants and the partial specific volumes were determined by the use of fluorescence quenching and density measurements, respectively. These polymeric surfactants were investigated as novel pseudostationary phases in micellar electrokinetic chromatography (MEKC) for the separation of chiral and achiral solutes. Solute hydrophobicity was found to have major influence on the MEKC retention of alkyl phenyl ketones. In contrast, hydrogen-bonding ability of benzodiazepines is the major factor that governs their retention, but hydrophobicity has an insignificant effect on MEKC retention of benzodiazepines.     

Novel anionic copolymerized surfactants of mixed achiral and chiral surfactants as pseudostationary phases for micellar electrokinetic chromatography

One disadvantage of amino acid-based chiral selectors for micellar electrokinetic chromatography (MEKC) is that either they have very low solubility or are insoluble at acidic pHs. In order to increase solubilities at lower pHs, we have synthesized a highly water-soluble achiral surfactant and copolymerized it with an amino acid-based chiral surfactant. These two surfactants were polymerized either separately or at various molar rations of binary solutions, yielding pure molecular or copolymerized surfactant (CoPS), respectively. All surfactants were characterized by use of several analytical techniques prior to using them as novel pseudostationary phases in MEKC. The chromatographic performance of the CoPS in MEKC was tested with chiral and achiral analytes. The highly soluble sulfate head group significantly increased the solubility of amino acid-based CoPS over a wide range of pH. Three chiral binaphthyl derivatives were tested and each surfactant system was found to have different selectivity.     

Analysis of glycopeptide antibiotics using micellar electrokinetic chromatography and borate complexation

Micellar electrokinetic chromatography (MEKC) was investigated as a technique for the separation and analysis of the following related glycopeptide antibiotics: alpha-avoparcin, beta-avoparcin, ristocetin A, ristocetin B and vancomycin. Sodium dodecyl sulfate (SDS) micelles were employed as the pseudostationary phase in conjunction with borate or CHES buffers at pH 9.2. A complete separation of the glycopeptides was achieved only when two separation mechanisms were employed simultaneously: (i) differential partitioning of the glycopeptides into SDS micelles; and (ii) differential complexation of the glycopeptides with the borate anion from the borate buffer. Quantitatively, linearity was confirmed for each antibiotic from 0.5 to 40 ppm, with correlation coefficients (r(2)) ranging from 0.9996 (vancomycin and beta-avoparcin) to 0.9986 (alpha-avoparcin). Detection limits ranging from 0.01 ppm (vancomycin) to 0.2 ppm (avoparcin) were achieved, and the mean recovery of avoparcin at the 10 ppm level was 99.2%.     

Macromolecular surfactant as a pseudo-stationary phase in micellar electrokinetic capillary chromatography

We examined polymers of sodium 11-acrylamidoundecanoate [poly(Na 11-AAU)] with a very high molecular mass (>10(6)) for their potential use as a pseudo-stationary phase in micellar electrokinetic capillary chromatography (MEKC). Size-exclusion chromatography and capillary electrophoresis studies reveal that the polymers are highly charged, and have a densely packed chain structure. For aromatic compounds, the polymeric surfactant showed significantly different selectivity than sodium dodecyl sulfate (SDS). It was suggested that one molecule of poly(Na 11-AAU) forms one micelle. The structural stability of this pseudo-stationary phase permitted its use with relatively high percentages of organic modifiers in the buffer medium, allowing the separation of highly hydrophobic compounds which are difficult to analyze by conventional MEKC with SDS.     

Polymers of sodium-N-undec-10-ene-1-oyl taurate and sodium-N-undec-10-ene-1-oyl aminoethyl-2-phosphonate as pseudostationary phases for electrokinetic chromatography

The use of micelle polymers, a class of polysoaps with a polymerized hydrophobic interior and a charged hydrophillic exterior, as pseudostationary phases in electrokinetic chromatography has generated significant interest. Their stable structure has been shown to provide significant advantages over conventional micelles when used as pseudostationary phases. In previous studies, micelle polymers have had carboxylate and sulfate head groups. These chemistries have limitations: carboxylate micelle polymers precipitate out of solution at pH less than seven or eight and sulfate head groups are not stable to hydrolysis and are hydrolyzed during polymerization. Additionally, while the chemical selectivity of conventional micelles varies with head group chemistry, no significant differences in chemical selectivity were observed between analogous polymers with sulfate and carboxylate groups. To overcome the limitations of carboxylate and sulfate head groups, and to further investigate the chemical selectivity of micelle polymers, poly(sodium-N-undec-10-ene-1-oyl-taurate) and poly(sodium-N-undec-10-ene-1-oyl-ethyl-2-phosphonate) micellar polymers have been synthesized and characterized as pseudostationary phases. These polymers have amide functionality and stable, strongly acidic sulfonate and phosphonate head groups. These polymers did provide improved solubility at low pH, and are stable under the conditions studied. The chromatographic performance and chemical selectivity of the polymers has been studied by several methods, including linear solvation energy relationships. Poly(sodiumN-undec-10-ene-1-oyl-taurate) has greater electrophoretic mobility than other polymers of this type, and can be used for the separation of hydrophobic compounds. The polymers do exhibit unique selectivity, but the differences in selectivity are not significant for the majority of compounds studied.     

Towards a general approach for the impurity profiling of drugs by micellar electrokinetic chromatography

A general micellar electrokinetic chromatographic (MEKC) strategy for the impurity profiling of drugs was developed involving a sodium dodecyl sulfate (SDS) and a cetyltrimethylammonium bromide (CTAB) MEKC system. With this combination, in principle, each sample component passes the detector in at least one of the two MEKC systems provided that separation buffers of the same pH are used in both systems. In order to select the proper MEKC systems, the electroosmotic flow (EOF) and micelle migration time (t(mc)) were determined for separation buffers of several pH values, containing various amounts of surfactant and organic modifier. The selectivity of the MEKC systems was studied using a mixture of compounds with a wide range of physico-chemical properties. The final selection of two adequate MEKC systems for this approach was based on the requirements that the t(mc) (i.e., analysis time) of both systems was below 20 min and that the t(mc)/t(eof) ratio was above 3 or 2 for the SDS and CTAB system, respectively. Furthermore, the systems should provide high efficiency, exhibit differences in selectivity and use moderate concentrations of modifier and surfactant, so that, if needed, further optimization is possible. The selected MEKC systems contained 60 mM SDS or 10 mM CTAB, respectively, in a phosphate buffer (pH 7.5) with 10% acetonitrile. Some test compounds with extreme mobilities were used to demonstrate the suitability of the MEKC approach to detect each component of a sample. The potential of the proposed MEKC combination for impurity profiling was demonstrated by the analysis of fluvoxamine with several impurities at the 0.1% level.     

Multivariate approach for the enantioselective analysis in MEKC‐MS: II. Optimization of 1,1′‐binaphthyl‐2,2′‐diamine in positive ion mode

Enantiomeric separation and detection of 1,1′‐binaphthyl‐2,2′‐diamine (BNA) has been successfully optimized by MEKC‐ESI‐MS using a polymeric surfactant polysodium N‐undecenoxycarbonyl‐L‐leucinate (poly‐L‐SUCL) as a pseudostationary phase. In the first step, MEKC conditions were optimized by a five‐factor three‐level central composite design (CCD) of experiment. All five MEKC factors (buffer pH, percentage of ACN in the running buffer, concentration of surfactant, concentration of ammonium acetate (NH₄OAc), and voltage) were found significant to the responses (measured as the chiral resolution and analysis time). The interactions between MEKC factors were further evaluated using a quadratic model equation which allowed the generation of 3‐D response surface image to reach the optimum conditions. To obtain the best S/N, sheath liquid composition and spray chamber parameters were successfully optimized using the same strategy. Baseline enantiomeric resolution in less than 20 min and optimum MS signal of BNA enantiomers (S/N = 45 at 0.4 mg/mL) were ultimately achieved at the optimized conditions. The adequacy of the model was validated by experimental runs at the optimal predicted conditions. The predicted results were found to be in good agreement with the experimental data.     

Cationic double-chained surfactant as pseudostationary phase in micellar electrokinetic capillary chromatography for drug separations

The cationic double-chained surfactant didodecyldimethylammonium bromide (DDAB) was used as pseudostationary phase (PSP) in micellar electrokinetic capillary chromatography (MEKC). Its performance on the three kinds of drugs, i.e., basic, acidic, and neutral drugs, was systematically investigated. Nicotine, cotinine, caffeine, lidocaine, and procaine were selected as the model basic drugs. Good baseline separation and high efficiency were obtained under the optimal separation condition that consisted of 50mM phosphate (pH 4.0) and 0.08 mM DDAB. Three basic phenylenediamine isomers can also be well separated with DDAB in buffer. In addition, DDAB can form cationic bilayer on the capillary wall, thus the wall adsorption of basic analytes was greatly suppressed. Compared with commonly used CTAB, the separation of basic drugs was significantly improved with a much lower amount of DDAB present in the buffer. The DDAB-involved MEKC also showed superiority to CTAB upon the separation of acidic drugs, amoxicillin and ampicillin. In the case of neutral compounds, a good separation of resorcinol, 1-naphthol and 2-naphthol was achieved with 0.1mM DDAB and 30% (v/v) acetonitrile (ACN) present in buffer. Hence, it was concluded that the double-chained cationic surfactant DDAB can be a good substitute for traditional single-chained surfactant CTAB in MEKC.     

Separation of aromatic hydrophobic sulfonates by micellar electrokinetic chromatography

Two different buffer systems for the separation of 12 aromatic hydrophobic sulfonates by micellar electrokinetic chromatography (MEKC) were developed. The following buffer systems were used: aqueous phosphate buffers containing either cetyltrimethylammonium bromide (CTAB) or sodium dodecyl sulfate (SDS). Eleven aromatic sulfonates were simultaneously separated in less than 35 min employing 20 mM phosphate buffer, pH 7.0 containing 50 mM SDS and 10% of acetonitrile.     

聚(苯乙烯-co-甲基丙烯酸)自组装胶束假固定相电动色谱的特性

研究了两亲性无规共聚物聚(苯乙烯-co-甲基丙烯酸)(P(St-co-MAA))(单体摩尔比分别为6:4和7:3)自组装胶束的物理化学性质,及其作为假固定相(PSP)的胶束电动色谱性能。测定了聚合物胶束的临界胶束浓度(CMC),对胶束内核微环境的极性、表面电荷密度和流体力学直径等微结构参数进行了表征,对时间窗口、亚甲基选择性等电动色谱参数进行了测定,并与聚(甲基丙烯酸甲酯-co-甲基丙烯酸)(P(MMA-co-MAA))胶束、十二烷基硫酸钠(SDS)胶束体系进行了比较;利用线性溶剂化能关系(LSER)研究了聚合物PSP的选择性差异。结果表明:P(St-co-MAA)体系具有最小的CMC、最宽的时间窗口和最好的亚甲基选择性;LSER表明,疏水作用是决定聚合物PSP选择性的最主要因素,氢键酸度其次,特别是P(St-co-MAA)(单体摩尔比7:3)体系具有最高的作用参数,显示了该PSP具有较高的分离选择性。     

Effect of Micelle Composition on Acidic Drugs Separation Behavior by Micellar Electrokinetic Capillary Chromatography

Micellar electrokinetic capillary chromatography (MECC) is a branch of capillary electrophoretic techniques, in which surfactant micelles are added to the electrolyte solution as pseudostationary phase. Separation in MECC is based on electrophoretic mobilities of the analytes when partitioned into micelles1. In this work, four acidic drugs similar in structure with aryl carboxylic acid were separated by MECC. The effects of type of surfactant, such as anionic surfactant SDS, nonionic …     

Separation of Six Pyridoncarboylxic Acid Derivatives by Micellar and Microemulsion Electrokinetic Chromatography

Micellar electrokinetic chromatography (MEKC) and microemulsion electrokinetic chromatography (MEEKC) are two kinds of electrokinetic capillary chromatography (EKC), which are characterized of high solubilization capacity and separation efficiency. In our previous work, some polar organic compounds and hydrophobic neutral compounds were separated successfully by EKC1-3. In this paper, these methods were used for separating six pyridoncarboylxic acid derivatives with similar structures. T…     

Cationic gemini surfactants as pseudostationary phases in micellar electrokinetic chromatography. Part I: Effect of head group

Two cationic gemini surfactants with pyrrolidinium or alkyl ammonium head groups with but-2-yne spacers, but with the same length hydrocarbon chain have been characterized with respect to their aggregation behaviors and separation power as pseudostationary phases (PSPs) for micellar electrokinetic chromatography (MEKC). They were compared with a commonly used PSP, sodium dodecylsulfate (SDS). The results suggest that the head groups of the surfactants have some effect on physicochemical properties such as critical micelle concentration (CMC), C₂₀, γ_CMC, partial specific volume, methylene selectivity and mobilities of the surfactants. CMC values of G1, G2 and SDS in pure water were found to be 0.82, 0.71, and 8.08 mM, respectively; they were reduced to 0.21, 0.11, and 3.0 mM when measured in 10 mM phosphate buffer at pH 7.0. G1 (α_CH2=2.74${\alpha }_{\text{C}{\text{H}}_2}=2.74$) and G2 (α_CH2=2.48${\alpha }_{\text{C}{\text{H}}_2}=2.48$) provided the most and the least hydrophobic environment, respectively. According to their partial specific volumes, geminis were found to have more flexible structures as compared with sodium dodecylsulfate. The effects of the head group structure were also characterized with the linear solvation energy relationship (LSER) model, which was able to evaluate the role of solute size, polarity/polarizability, and hydrogen bonding on retention and selectivity. The cohesiveness, hydrogen bond acidic and basic character of the surfactant systems were found to have the most significant influence on selectivity and MEKC retention of the gemini surfactants. It should be noted that with their large positive coefficient a values, G1 and G2 were found to be stronger HB acceptors than anionic and most of the cationic surfactants studied in the literature.     

Characterization of surfactant and phospholipid vesicles for use as pseudostationary phases in electrokinetic chromatography

The physical, electrophoretic and chromatographic properties (mean diameter, electroosmotic flow, electrophoretic mobility, elution range, efficiency, retention, and hydrophobic, shape, and chemical selectivity) of three surfactant vesicles and one phospholipid vesicle were investigated and compared to a conventional micellar pseudostationary phase comprised of sodium dodecyl sulfate (SDS). Chemical selectivity (solute-pseudostationary phase interactions) was discussed from the perspective of linear solvation energy relationship (LSER) analysis. Two of the surfactant vesicles were formulated from nonstoichiometric aqueous mixtures of oppositely charged, single-tailed surfactants, either cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS) in a 3:7 mole ratio or octyltrimethylammonium bromide (OTAB) and SDS in a 7:3 mole ratio. The remaining surfactant vesicle was comprised solely of bis(2-ethylhexyl)sodium sulfosuccinate (AOT) in 10% v/v methanol, and the phospholipid vesicle consisted of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and phosphatidyl serine (PS) in 8:2 mole ratio. The mean diameters of the vesicles were 76.3 nm (AOT), 86.9 nm (CTAB/SOS), 90.1 nm (OTAB/SDS), and 108 nm (POPC/PS). Whereas the coefficient of electroosmotic flow (10(-4) cm2 V(-1) s(-1)) varied considerably (1.72 (OTAB/SDS), 3.77 (CTAB/SOS), 4.05 (AOT), 5.26 (POPC/PS), 5.31 (SDS)), the electrophoretic mobility was fairly consistent (-3.33 to -3.87 x 10(-4) cm2 V(-1) s(-1)), except for the OTAB/SDS vesicles (-1.68). This resulted in elution ranges that were slightly to significantly larger than that observed for SDS (3.12): 3.85 (POPC/PS), 8.6 (CTAB/SOS), 10.1 (AOT), 15.2 (OTAB/SDS). Significant differences were also noted in the efficiency (using propiophenone) and hydrophobic selectivity; the plate counts were lower with the OTAB/SDS and POPC/PS vesicles than the other pseudostationary phases (< or = 75,000/m vs. > 105,000/m), and the methylene selectivity was considerably higher with the CTAB/SOS and OTAB/SDS vesicles compared to the others (ca. 3.10 vs. < or = 2.6). In terms of shape selectivity, only the CTAB/SOS vesicles were able to separate all three positional isomers of nitrotoluene with near-baseline resolution. Finally, through LSER analysis, it was determined that the cohesiveness and hydrogen bond acidity of these pseudostationary phases have the greatest effect on solute retention and selectivity.