Multi-criteria decision making in micellar liquid chromatographic separation of chlorophenols

Simultaneous optimization of separation quality and analysis time of the micellar liquid chromatography of nine chlorophenol isomers was investigated. The effect on retention of three experimental parameters was studied using multivariate analysis. The factors studied were the concentration of sodium dodecyl sulfate, propanol content, and pH of the mobile phase. The experiments were performed according to the face-centered cube central composite design and the inverse form of the experimental retention times of analytes was fitted to polynomial models. The results of the analysis of variance showed that the models obtained explain over 99% of the variance observed in the chromatograms. The good predictive ability of the models was verified by high correlation coefficient (R2 > 0.99) and F ratio values for the plots of predicted cross-validated versus experimental retention times. The study showed that the use of the Pareto-Optimality method, an approach from multi-criteria decision making, allows selection of the best possible combinations of separation quality and analysis time in micellar liquid chromatography of chlorophenols.     

SDS-Based Biomembrane Mimetic Chromatography for Prediction of Human Drug Transport as an in Vitro Technique

The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k _BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R ² = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R ² = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.     

Heteroscedasticity of retention factor and adequate modeling in micellar liquid chromatography

The two concepts of micelle formation (pseudo-phase and mass-action) could be the basis of retention models in micellar liquid chromatography (MLC). The separation of 4-hydroxybenzoic acid esters and seven polyaromatic hydrocarbons were performed to study the repeatability of retention factor in MLC. The full two factor experimental design was used for studying the dependence of retention factor variance on mobile phase composition (sodium dodecylsulfate, 1-butanol). The experimentally observed heteroscedasticity and perturbations after linearization were taken into account by using statistical weights obtained on the basis of errors propagation law and the modeling of retention by non-weighted and weighted least squares method was performed. The mechanistical retention models based on pseudo-phase and mass-action concepts of micelle formation were compared by fitting quality and prediction capability and high robustness of bilogarithmic dependence was observed. The significance of retention factor heteroscedasticity for retention hydrophobicity relationships was shown.     

Separation optimization of quercetin,hesperetin and chrysin in honey by micellar liquid chromatography and experimental design

The chemometrics approach was applied for the separation optimization of flavonoid markers (quercetin, hesperetin and chrysin) in honey using micellar liquid chromatography (MLC). The investigated method combines SPE of flavonoids from honey using C₁₈ cartridge and their separation and quantification by micellar liquid chromatography. A two level full factorial design was carried out to evaluate the effect of four experimental factors including concentration of SDS, alkyl chain length of the alcohol used as the organic modifier (N), volume percentage of the organic modifier (V_m) and volume percentage of acetic acid (AcOH) in mobile phase on analytes retention times. Experiments for analytes retention times modeling and optimization of separation were performed according to central composite design. Multiple linear regression method was used for the construction of the best model based on experimental retention times. Pareto optimal method was used to find suitable compatibility between resolution and analysis time of analytes in honey. The optimum mobile phase composition for separation and determination of analytes in honey were [SDS]=0.124 mol/L; 7.8% v/v ethanol and 5.0% v/v AcOH. Limits of detection and linear range of flavonoid markers were 0.0079–0.0126, 0.05–50.0 mg/L, respectively.     

SDS-Based Biomembrane Mimetic Chromatography for Prediction of Human Drug Transport as an in Vitro Technique

The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k _BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R ² = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R ² = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.

     

New Perspectives in Micellar Liquid Chromatography

Abstract

This paper will summarize several new findings obtained in our laboratory on the use of micellar mobile phases in liquid chromatography. The topics to be addressed include (i) stationary phase modification by the mobile phase surfactant in micellar liquid chromatography, (ii) investigation of the retention mechanism in micellar liquid chromatography (MLC) using an alkyl-benzene homologous series, (iii) evaluation of the effects of organic additives upon retention and efficiency in MLC, and (iv) preliminary characterization of several new classes of surfactant molecules for use in MLC. The information gained from these studies provides new insights into the dynamics of MLC and demonstrates their potential usefulness in several new separation applications including the resolution of optical isomers.     

Development of predictive quantitative retention–activity relationship models of alkaloids by mixed micellar liquid chromatography

The mixed micellar liquid chromatography is a mode that uses mixed micellar system of Brij35/SDS (85 : 15) as a mobile phase under adequate experimental conditions, can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged. In this article, the applications of biopartitioning micellar chromatography, using mixed micellar system to describe and estimate bioactivities of alkaloids, has been focused. The BMC_Brij35/SDS‐QRAR models of half‐life time, volume of distribution, plasma clearance and area under concentration–time curve were obtained using Brij35‐SDS retention data. The aim is to take a look at the capability of the mixed micellar liquid chromatography model to describe and/or estimate the bioactivity of alkaloids. Copyright © 2009 John Wiley & Sons, Ltd.     

Micellar-mediated shifts of ionization constants of amino acids and peptides

The acid-base dissociation constants, K_a, of amino acids and small peptides were determined in both aqueous and micellar solutions of sodium dodecyl sulfate and cetyltrimethylammonium bromide by potentiometric and chromatographic means. The observed differences in pK_a values between micellar media and aqueous solutions ranged between 0.23 and 2.21 units. The micellar-mediated pK_a shifts can be attributed to different solute-micelle interactions, mainly hydrophobic and electrostatic forces. The implications of the change in acid-base behavior on separation selectivity in micellar liquid chromatography and micellar electrokinetic capillary chromatography are discussed.     

1-Hexadecyl-3-methylimidazolium Ionic Liquid as a New Cationic Surfactant for Separation of Phenolic Compounds by MEKC

The ionic liquid 1-hexadecyl-3-methylimidazolium bromide ([C₁₆MIm]Br) has been used as a novel cationic surfactant for separation of phenolic compounds, including quinol, phloroglucinol, resorcinol, phenol, p-cresol, and m-nitrophenol, by micellar electrokinetic capillary chromatography (MEKC). The effects of buffer concentration and pH, concentration of [C₁₆MIm]Br, and applied potential were studied. Use of the optimized buffer (25 mmol L^?1 NaH₂PO₄), 10 mmol L^?1 [C₁₆MIm]Br, and an applied potential of ?15 kV enables optimum separation with regard to resolution and migration time. The phenolic compounds were detected at 214 nm. The micelle of this long-alkyl-chain imidazolium ionic liquid acts as a pseudo-stationary phase in this MEKC separation.     

Simultaneous Optimization of Surfactant Concentration and Organic Modifier in Micellar Liquid Chromatography. Application to the Separation of Phenolic Compounds

ABSTRACT

The separation selectivity of eighteen phenolic derivatives in micellar high-performance liquid chromatography was studied as a function of parameters on which it depends: surfactant and organic modifier concentration. The surfactant used in this study was cetyltrimethylammonium bromide, and as organic modifier methanol. An iterative regression optimization strategy for these two parameters has been used. The equation that best explains the experimental

results is 1/k' = A +Bμ + Cφ + DμΦ. We propose the use of this model in conjunction with the appropriate factorial design to predict the solute retention behaviour in micellar liquid chromatography with hibrid eluents.     

Optimization of artificial neural network for retention modeling in high-performance liquid chromatography

An artificial neural network (ANN) model for the prediction of retention times in high-performance liquid chromatography (HPLC) was developed and optimized. A three-layer feed-forward ANN has been used to model retention behavior of nine phenols as a function of mobile phase composition (methanol-acetic acid mobile phase). The number of hidden layer nodes, number of iteration steps and the number of experimental data points used for training set were optimized. By using a relatively small amount of experimental data (25 experimental data points in the training set), a very accurate prediction of the retention (percentage normalized differences between the predicted and the experimental data less than 0.6%) was obtained. It was shown that the prediction ability of ANN model linearly decreased with the reduction of number of experiments for the training data set. The results obtained demonstrate that ANN offers a straightforward way for retention modeling in isocratic HPLC separation of a complex mixture of compounds widely different in pK_a and log K_ow values.     

Separation of a group of N-phenylpyrazole derivatives by micellar electrokinetic chromatography: application to the determination of solute-micelle association constants and estimation of the hydrophobicity

Micellar electrokinetic chromatography (MEKC) was applied to the separation of a group of N-phenylpyrazole derivatives. Sodium dodecyl sulfate (SDS) as micellar system and 2-(N-cyclohexylamino)ethanesulfonic acid (CHES) as separation buffer (pH 10) were employed in the absence and presence of different percentages of medium chain alcohols (n-propanol or n-butanol). The separation of multicomponent mixtures of the solutes studied enabled the rapid determination of their retention factors which, in turn, allowed the study of the separation selectivity of compounds and the determination of their solute-micelle association constants (from the linear variation of the retention factors as a function of the total surfactant concentration in the separation buffer). Separation selectivity was studied according to the elution range and number of solutes separated in all the electrolyte solutions employed (45 micellar phases). The effect of the buffer concentration (0.05, 0.08 and 0.10 M), the alcohol nature (n-propanol or n-butanol) and the alcohol percentage (1, 3 or 5%) of the values obtained for the solute-micelle association constants was also studied. The best separation (12 solutes) was performed when a 0.08 M CHES buffer, pH 10, 0.02 M SDS modified by 5% n-butanol was used. The possibilities of using MEKC for evaluating the hydrophobicity of compounds was investigated through the study of the correlation between the logarithm of the retention factors of N-phenylpyrazole derivatives and their logarithm of the octanol-water distribution coefficients estimated by high performance liquid chromatography (HPLC).     

Additivity of statistical moments in the exponentially modified Gaussian model of chromatography

A homologous series of saturated fatty acids ranging from C₁₀ to C₂₂ was separated by reversed-phase capillary liquid chromatography. The resultant zone profiles were found to be fit best by an exponentially modified Gaussian (EMG) function. To compare the EMG function and statistical moments for the analysis of the experimental zone profiles, a series of simulated profiles was generated by using fixed values for retention time and different values for the symmetrical (σ) and asymmetrical (τ) contributions to the variance. The simulated profiles were modified with respect to the integration limits, the number of points, and the signal-to-noise ratio. After modification, each profile was analyzed by using statistical moments and an iteratively fit EMG equation. These data indicate that the statistical moment method is much more susceptible to error when the degree of asymmetry is large, when the integration limits are inappropriately chosen, when the number of points is small, and when the signal-to-noise ratio is small. The experimental zone profiles were then analyzed by using the statistical moment and EMG methods. Although care was taken to minimize the sources of error discussed above, significant differences were found between the two methods. The differences in the second moment suggest that the symmetrical and asymmetrical contributions to broadening in the experimental zone profiles are not independent. As a consequence, the second moment is not equal to the sum of σ² and τ², as is commonly assumed. This observation has important implications for the elucidation of thermodynamic and kinetic information from chromatographic zone profiles.     

High‐performance liquid chromatography separation of unsaturated organic compounds by a monolithic silica column embedded with silver nanoparticles

The optimization of a porous structure to ensure good separation performances is always a significant issue in high‐performance liquid chromatography column design. Recently we reported the homogeneous embedment of Ag nanoparticles in periodic mesoporous silica monolith and the application of such Ag nanoparticles embedded silica monolith for the high‐performance liquid chromatography separation of polyaromatic hydrocarbons. However, the separation performance remains to be improved and the retention mechanism as compared with the Ag ion high‐performance liquid chromatography technique still needs to be clarified. In this research, Ag nanoparticles were introduced into a macro/mesoporous silica monolith with optimized pore parameters for high‐performance liquid chromatography separations. Baseline separation of benzene, naphthalene, anthracene, and pyrene was achieved with the theoretical plate number for analyte naphthalene as 36 000 m^?1. Its separation function was further extended to cis/trans isomers of aromatic compounds where cis/trans stilbenes were chosen as a benchmark. Good separation of cis/trans‐stilbene with separation factor as 7 and theoretical plate number as 76 000 m^?1 for cis‐stilbene was obtained. The trans isomer, however, is retained more strongly, which contradicts the long‐ established retention rule of Ag ion chromatography. Such behavior of Ag nanoparticles embedded in a silica column can be attributed to the differences in the molecular geometric configuration of cis/trans stilbenes.     

Determination of Natural and Synthetic Endocrine-Disrupting Chemicals (EDCs) in Sewage Based on SPE and MEKC with Amperometric Detection

An integrated analytical method to monitor five environmental endocrine disrupting chemicals (EDCs): 2,4-dichlorophenol (DCP), 4-tert-butylphenol (BP), bisphenol A (BPA), 17α-ethynylestradiol (EE2) and 4-n-nonylphenol (NP), was developed for the first time, based on a solid-phase extraction and miniaturized micellar electrokinetic chromatography with amperometric detection. In order to get the optimum conditions of their separation and detection, several parameters including pH and concentration of running buffer, concentration of micelle, separation voltage and injection time were studied and optimized. The five EDCs were well separated under the optimum conditions within 12 min. This method was successfully applied for the determination of these five EDCs in sewage influent sample. Satisfactory extraction performances from sewage sample was obtained by solid-phase extraction, using a C₁₈ cartridge. Quantitative analysis showed that DCP, BP, and BPA existed at μg L^?1 level in the selected sample, while EE2 and NP were not detected.