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A Berthod

Publications and source records attributed to A Berthod.

At least 19 recordsLinked to original sources
PubMed2005

Ionic liquids versus triethylamine as mobile phase additives in the analysis of beta-blockers.

A comparative study of peak shape, elution behavior, elution strength and resolution of seven beta-blockers (acebutolol, alprenolol, labetalol, metoprolol, nadolol, pindolol and propranolol) chromatographed with aqueous-organic mobile phases containing additives such as the ionic liquid (IL) 1-butyl-3-methylimidazolium (BMIM BF(4)) or triethylamine (TEA) is performed using a conventional reversed-phase Kromasil C(18) column and isocratic elution. The efficiencies and asymmetry factors achieved for the group of beta-blockers in the Kromasil C(18) column improve when the cationic modifiers are added to the aqueous-organic mobile phase as competing additives for the silanol active sites. BMIM BF(4) is a significantly better additive compared to TEA. The improvement is more notably for the asymmetry factor, BMIM BF(4) allowing to obtain higher plate numbers than TEA at the same concentration. The effects of both modifiers on elution strength and retention factors are, however, different. TEA decreases the solute retention factors when BMIM BF(4) does not change them significantly. Using other additives taken in the IL family such as 1-butyl-3-methylimidazolium hexafluorophosphate and 1-octyl-3-methylimidazolium tetrafluoroborate (OMIM BF(4)), it is shown that the silanol screening effect is always observed, due to the IL cation, when it is possible to increase or to decrease the solute retention factors playing with the hydrophobic nature or chaotropic character of its anion.

Adrenergic beta-Antagonists↗
PubMed2005

Alkane effect in the Arizona liquid systems used in countercurrent chromatography.

Countercurrent chromatography (CCC) is a separation technique that uses a biphasic liquid system; one liquid phase is the mobile phase, the other liquid phase is the stationary phase. Selection of the appropriate liquid system can be a problem in CCC, since it is necessary to select both the "column" and the mobile phase at the same time as the first is completely dependent on the second. A range of systems with various proportions of solvents were developed to ease this choice; 23 variations of the heptane/ethyl acetate/methanol/water biphasic liquid system were labeled A to Z. This range proved to be extremely useful and became the popular Arizona (AZ) liquid system. However, authors often replace the heptane with hexane. In this work, the chemical compositions of the upper phases and the lower phases of 55 Arizona systems made with various alkanes (pentane, hexane, heptane, isooctane and cyclohexane) were determined by gas chromatography and Karl Fischer titration. The test mixture separated consisted of five steroid compounds. The lower phases were found to have similar compositions when different alkanes were used, but the upper phases were found to change. Exchanging heptane for hexane or isooctane produced minimal changes in the CCC chromatogram, while changing the proportions of the solvents resulted in an exponential change in the retention volumes. The high density of cyclohexane made liquid stationary phase retention difficult. All Arizona systems equilibrated within 30 min, but were not stable: water slowly hydrolyzed the ethyl acetate (as shown by a continuous decrease in the pH of the lower aqueous phase), especially in the water-rich systems (early alphabet letters).

Acetates↗
PubMed2005

Effect of ionization and the nature of the mobile phase in quantitative structure-retention relationship studies.

The octanol-water distribution constant, commonly called partition coefficient, Po/w, is a parameter often retained as a measure of the hydrophobicity of a molecule. log Po/w, for a given molecule, can be conveniently evaluated constructing correlation lines between standard retention factor logarithms (log k) in reversed-phase liquid chromatography (RPLC) and standard log Po/w values. Many compounds of pharmaceutical interest can be quite hydrophobic and have, simultaneously, basic nitrogen atoms or acidic sulfur containing groups in their structure. This renders them ionizable. The hydrophobicity of the molecular drug form (Po/w value) is completely different from its ionic form (log Po/w(+ or -) value). The actual hydrophobicity of such ionizable molecule depends on the pH. It can be represented by an apparent Papp value that takes into account the amount of compound in its molecular and ionic state combining the Po/w and Po/w(+ or -) values. In this work, log k in RPLC for ionizable as well as non-ionizable pharmaceutical compounds with different therapeutic properties (10 beta-blockers, seven tricyclic antidepressants (TA), eight steroids and 12 sulfonamides) were correlated with log Po/w. Similar correlations were done between log k and the corrected log Papp values at pH 3. Aqueous-organic mobile phases containing acetonitrile (conventional RPLC) and micellar-organic mobile phases (micellar liquid chromatography, MLC), prepared with the anionic surfactant sodium dodecyl sulfate and the organic solvents acetonitrile, propanol or pentanol, were also used to elute the compounds. All mobile phases were buffered at pH 3. Using conventional retention RPLC data, the correlation of log k with log Po/w, was satisfactory for steroids because they cannot ionize. For ionizable beta-blockers and TAs, the use of log Papp values improved the quality of the correlations, but yielded similar results for sulfonamides. In MLC, since an electrostatic interaction is added to hydrophobic forces, poorer correlations were obtained in all cases. The retention data obtained in RPLC also seems to correlate better with the biological activity of the drugs.

Chromatography, Liquid↗
PubMed2004

Use of the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate in countercurrent chromatography.

Room temperature ionic liquids (RTIL) are molten salts that are liquids at room temperature. Their liquid state makes them possible candidates as solvents in countercurrent chromatography (CCC), which uses solvents as both the mobile and stationary phases. The study focuses on 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM PF(6)), an easy to synthesize and purify RTIL whose melting point is -8 degrees C. It is shown that BMIM PF(6) behaves like a solvent of significant polarity (comparable with that of ethanol). The ternary phase diagram water-acetonitrile-BMIM PF(6) is given, because it was necessary to add acetonitrile to reduce the ionic liquid viscosity. The 40:20:40% w/ w water-acetonitrile-BMIM PF(6) biphasic liquid system was found to be appropriate as a biphasic liquid system for CCC. Different aromatic solutes, including bases, acids, and neutral compounds, were injected into the CCC column to estimate their distribution constants between the ionic liquid-rich phase and the aqueous phase. The resulting K(il/w) constants were compared with the corresponding literature octanol-water partition coefficients, K(o/w). The important drawbacks in the use of RTIL in CCC are clearly pointed out: high viscosity producing pressure build-up, UV absorbance limiting the use of the convenient UV detector, and non-volatility precluding the use of the evaporative light-scattering detector for continuous detection.

Countercurrent Distribution↗
PubMed2004

Countercurrent chromatographic separation: a hydrodynamic approach developed for extraction columns.

In countercurrent chromatography (CCC) both stationary and mobile liquids undergo intense mixing in the variable force field of a coil planet centrifuge and the separation process, like the separation in conventional solvent extraction column, is influenced by longitudinal mixing in the phases and mass transfer between them. This paper describes how the residence time distribution (or the elution profile) of a solute in CCC devices and the interpretation of experimental peaks, can be described by a recently developed cell model of longitudinal mixing. The model considers a CCC column as a cascade of perfectly mixed equal-size cells, the number of which is determined by the rates of longitudinal mixing in the stationary and mobile phases. Experiments were carried out to demonstrate the validation of the model and the possibility of predicting the partitioning behaviour of the solutes. The methods for estimating model parameters are discussed. Longitudinal mixing rates in stationary and mobile phases have been experimentally determined and experimental elution profiles are compared with simulated peaks. It is shown that using the cell model the peak shape for a solute with a given distribution constant can be predicted from experimental data on other solutes.

Countercurrent Distribution↗
PubMed2004

Determination of liquid-liquid partition coefficients by separation methods.

By essence, all kinds of chromatographic methods use the partitioning of solutes between a stationary and a mobile phase to separate them. Not surprisingly, separation methods are useful to determine accurately the liquid-liquid distribution constants, commonly called partition coefficient. After briefly recalling the thermodynamics of the partitioning of solutes between two liquid phases, the review lists the different methods of measurement in which chromatography is involved. The shake-flask method is described. The ease of the HPLC method is pointed out with its drawback: the correlation is very sensitive to congeneric effect. Microemulsion electrokinetic capillary electrophoresis has become a fast and reliable method commonly used in industry. Counter-current chromatography (CCC) is a liquid chromatography method that uses a liquid stationary phase. Since the CCC solute retention volumes are only depending on their partition coefficients, it is the method of choice for partition coefficient determination with any liquid system. It is shown that Ko/w, the octanol-water partition coefficients, are obtained by CCC within the -1 < log Ko/w < 4 range, without any correlation or standardization using octanol as the stationary phase. Examples of applications of the knowledge of liquid-liquid partition coefficient in the vast world of solvent extraction and hydrophobicity estimation are presented.

Chemical Phenomena↗
PubMed2004

Micellar versus hydro-organic mobile phases for retention-hydrophobicity relationship studies with ionizable diuretics and an anionic surfactant.

Logarithm of retention factors (log k) of a group of 14 ionizable diuretics were correlated with the molecular (log P o/w) and apparent (log P(app)) octanol-water partition coefficients. The compounds were chromatographed using aqueous-organic (reversed-phase liquid chromatography, RPLC) and micellar-organic mobile phases (micellar liquid chromatography, MLC) with the anionic surfactant sodium dodecyl sulfate (SDS), in the pH range 3-7, and a conventional octadecylsilane column. Acetonitrile was used as the organic modifier in both modes. The quality of the correlations obtained for log P(app) at varying ionization degree confirms that this correction is required in the aqueous-organic mixtures. The correlation is less improved with SDS micellar media because the acid-base equilibriums are shifted towards higher pH values for acidic compounds. In micellar chromatography, an electrostatic interaction with charged solutes is added to hydrophobic forces; consequently, different correlations should be established for neutral and acidic compounds, and for basic compounds. Correlations between log k and the isocratic descriptors log k(w), log k(wm) (extrapolated retention to pure water in the aqueous-organic and micellar-organic systems, respectively), and psi0 (extrapolated mobile phase composition giving a k = 1 retention factor or twice the dead time), and between these descriptors and log P(app) were also satisfactory, although poorer than those between log k and log P(app) due to the extrapolation. The study shows that, in the particular case of the ionizable diuretics studied, classical RPLC gives better results than MLC with SDS in the retention hydrophobicity correlations.

Chromatography, High Pressure Liquid↗
PubMed2003

pH dependence of the hydrophobicity of beta-blocker amine compounds measured by counter-current chromatography.

The octanol-water partition coefficients (Poct) of 17 antiadrenergic beta-blocker compounds were determined by counter-current chromatography (CCC). Since CCC uses a biphasic liquid system, the octanol-water liquid system was used with essentially an octanol stationary phase and aqueous buffer mobile phase. The Poct coefficients were obtained directly without any extrapolation. The measured Poct values were in the 0.0015-4070 range (-2.8 < log Poct < 3.6). Since the beta-blocking agents are ionizable compounds, the Poct values obtained were strongly dependent on the aqueous-phase pH. The apparent Poct coefficients of the beta-blockers were determined at three different pH values (approximately 3, 7 and 11) using 0.01 M ammonium phosphate buffers saturated with octanol. A model allowed us to obtain the molecular and ionic Poct value using the solute pKa with these three experimental octanol-water coefficients. Often, the Poct coefficients of the molecular forms obtained with the CCC method differ significantly from computed literature values and/or experimental values obtained by extrapolation. Relationships between biological properties and hydrophobicity were also examined.

Adrenergic beta-Antagonists↗
PubMed2003

Solvent properties of the 1-butyl-3-methylimidazolium hexafluorophosphate ionic liquid.

1-Butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF(6)) was synthesized and purified to be used as a ionic liquid solvent. Its physicochemical properties were studied. The ionic liquid/water (P(il/water)) and ionic liquid/heptane (P(il/heptane)) distribution coefficients of a set of 40 compounds with various functionalities, including organic acids, organic bases, amino acids, antioxidants, and neutral compounds, were measured using liquid chromatography. For ionizable compounds, the P(il/water) values measured at pH 2, 5.1, and 10 were very different. These allowed the determination of both the molecular P(o)il(/water) values and the ion P(-)il(/water) value for each compound. These coefficients were compared to the corresponding P(oct/water) coefficients. Marked differences in the partitioning behavior of basic, acidic, and neutral compounds were observed. The relationship between P(il/water) and P(oct/water) is different from that reported previously. By using the linear free energy solvation approach and the descriptors found for 12 solutes, the BMIM-PF(6) solvent parameters were calculated for the ionic liquid/water and ionic liquid/heptane biphasic systems. The regression parameters show a low basicity of the BMIM-PF(6) solvent compared to octanol. The high cohesion of the ions in the ionic liquid phase is also indicated by the regression equations obtained. Ionized phenols (phenoxide ions) associate more strongly with BMIM-PF(6) than most other ionized molecules. Amino acids were not soluble in ionic liquid; however, it is possible to extract them partially by adding a crown ether to the ionic liquid phase and working at pH 1. The positive form of amino acids is complexed by the crown ether and the complex is extracted in the ionic liquid phase.

Antioxidants↗
PubMed2001

Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange.

Teicoplanin is a macrocyclic glycopeptide that is highly effective as a chiral selector for LC enantiomeric separations. Two possible interaction paths were investigated and related to solute retention and selectivity: (1) interactions with the only teicoplanin amine group and (2) role of hydrogen bonding interactions. Mobile phases containing 0.5 and 5 mM copper ions were used to try to block the amine group. In the presence of copper ions, it was found that the teicoplanin stationary phase has a decreased ability to separate most underivatized racemic amino acids. However, it maintained its ability to separate enantiomers that were not alpha-amino acids. It is established that there is little copper-teicoplanin complex formation. The effect of Cu2+ on the enantioseparation of some alpha-amino acids appears to be due to the fact that these solutes are good bidentate ligands and form complexes with copper ions in the mobile phase. Isotopic exchange with deuterium oxide was performed using acetonitrile-heavy water mobile phases. It was found that the retention times of all amino acids were lower with deuterated mobile phases. The retention times of polar or apolar molecules without amine groups were higher with deuterated mobiles phases. In all cases, the enantioselectivity factors were unaffected by the deuterium exchange. It is proposed that the electrostatic interactions are decreased in the deuterated mobile phases and the solute-accessible stationary-phase volume is somewhat swollen by deuterium oxide. The balance of these effects is a decrease in the amino acid retention times and an increase in the apolar solute retention time. The enantioselectivity factors of all of the molecules remain unchanged because all of the interactions are changed equally. We propose a new global quality criterion (the E factor) for comparing and evaluating enantiomeric separations.

Amino Acids↗
PubMed2001

Nonionic micellar liquid chromatography coupled to immobilized enzyme reactors.

Immobilized enzyme reactors are used as post-column reactors to modify the detectability of analytes. An immobilized amino acid oxidase reactor was prepared and coupled to an immobilized peroxidase reactor to detect low level of amino acids by fluorescence of the homovanilic dimer produced. A cholesterol oxidase reactor was prepared to detect cholesterol and metabolites by 241 nm UV absorbance of the enone produced. The preparation of the porous glass beads with the immobilized enzymes is described. Micellar liquid chromatography is used with non-ionic micellar phases to separate the amino acids or cholesterol derivatives. It is demonstrated that the non ionic Brij 35 micellar phases are very gentle for the enzyme activity allowing the reactor activity to remain at a higher level and for a much longer time than with hydro-organic classical chromatographic mobile phases or aqueous buffers. The coupling of nonionic micellar phases with enzymatic detection gave limits of detection of 32 pmol (4.8 ng injected) of methionine and 50 pmol (19 ng injected) of 20alpha-hydroxy cholesterol. The immobilized enzyme reactors could be used continuously for a week without losing their activity. It is shown that the low efficiency obtained with micellar liquid chromatography is compensated by the possibility offered by the technique to easily adjust selectivity.

1-Propanol↗
PubMed2001

Covalently bound ionene polyelectrolyte-silica gel stationary phases for HPLC.

Micelle-mimetic ionene-based stationary phases for high-performance liquid chromatography (HPLC) are prepared by attaching [3,16]- and [3,22]-ionenes to aminopropyl silica through a carbon-nitrogen bond. These [x,y]-ionenes are polyelectrolytic molecules consisting of dimethylammonium charge centers interconnected by alternating alkyl chain segments containing x and y methylene groups, some of which can form aggregate species whose properties mimic those of conventional surfactant micelles. These ionene-bonded stationary phases were characterized using different recommended HPLC test mixtures. Test solute chromatographic behavior on the ionene phases was found to be similar to that of intermediate oligomeric or polymeric C-18 and/or phenyl phases, depending upon the specific test mixture employed. In addition, the phases exhibit significant solute shape recognition ability. The ionene stationary phases were successfully employed for the separation of the components of the recommended ASTM reversed-phase test mixture, as well as for ortho-, meta- and para-disubstituted benzenes and other positional or geometric isomeric compounds. The ionene materials allow for chromatographic separations under either reversed-phase or ion-exchange conditions. The retention mechanism on these multimodal phases can occur by hydrophobic partitioning or electrostatic interactions, depending upon the characteristics of the components of the analyte mixture (neutral or anionic). The effects of alteration of the percent organic modifier, flow rate and temperature of the mobile phase on chromatographic retention and efficiency on these phases were briefly examined.

Journal Article↗
PubMed2000

Test to evaluate countercurrent chromatographs. Liquid stationary phase retention and chromatographic resolution.

Countercurrent chromatography (CCC) is a liquid chromatography (LC) technique with a special column able to retain a liquid stationary phase while the liquid mobile phase is pumped through. The coil planet centrifuge machines are made of open tube wound on spools. A simple test is proposed. The methanol-water (90:10, v/v)-heptane biphasic system is used with heptane as the mobile phase in the ascending or tail-to-head mode. The methanol-water stationary phase retention volume is measured at different flow-rates and rotor rotation speeds. After every machine equilibration, an alkylbenzene mixture is injected and the retention factors, peak efficiencies and resolution factors are measured or calculated for each solute. The wealth of information contained in the data set obtained is demonstrated. Four coil planet centrifuge machines of very different characteristics and one hydrostatic CCC machine with channels and ducts were submitted to the test. It was shown that the Sf, stationary retention factor, obtained with these machines was linearly dependent on the square root of F, the mobile phase flow-rate [Q. Du, C. Wu, G. Qian, P. Wu, Y. Ito, J. Chromatogr. A 835 (1999) 231-235]. It is shown that the slopes of the Sf versus F(1/2) lines could be related to a minimum rotor rotation, omega(mini), necessary to obtain the hydrodynamic equilibrium. The Sf and F parameters give the mobile phase linear velocity, u. It is shown that u is proportional to the square root of omega, the rotor rotation speed. The slope and intercept of the latter relationship also result in an omega(mini) value coherent with the first one. With the peak efficiencies and chromatographic resolution factors obtained for toluene and hexylbenzene, the parameters: number of plates per tubing turn, machine volume for one plate, and tubing length for one plate, were calculated and compared for the five machines. The internal diameter of the tubing used is shown to be a critical parameter acting on the machine volume and number of tubing turns.

Benzene↗
PubMed2000

Evaluation of the macrocyclic glycopeptide A-40,926 as a high-performance liquid chromatographic chiral selector and comparison with teicoplanin chiral stationary phase.

A new macrocyclic antibiotic of the vancomycin family, referred to by its industrial designation as A-40,926, was bonded to 5 microm silica particles and utilised as a chiral stationary phase (CSP). Since A-40,926 is structurally related to teicoplanin, the A-40,926 CSP was compared to a commercially available teicoplanin CSP. A set of 28 chiral compounds, including amino-acids and related compounds, compounds with a ring containing the stereogenic centre, compounds bearing aromatic structures near their stereogenic centres and alcohols, was tested for enantioseparation on the two CSPs. The results are compared and discussed in terms of enantioselective Gibbs energy difference. The A-40,926 CSP was able to resolve one compound that was not resolved by the teicoplanin CSP. However, it could not separate four compounds that the teicoplanin CSP did separate. It is shown that the A-40,926 CSP is complementary to the teicoplanin CSP, thereby enlarging the number of enantiomers that can be separated by the macrocyclic glycopeptide based CSPs.

Anti-Bacterial Agents↗
PubMed2000

Effect of a variety of organic additives on retention and efficiency in micellar liquid chromatography

The effect of 21 organic additives (alkanols, alkane diols, dipolar aprotic solvents, alkanes) on the chromatographic behavior (retention, elution strength, efficiency) of probe solutes of widely differing hydrophobicity, such as benzene and 2-ethylanthraquinone, have been examined using a C18 stationary phase and sodium dodecyl sulfate (SDS) micellar mobile phases. The mobile-phase elution strength parallels the octanol-water partition coefficients of the additives or their ability to bind to the SDS micellar system, due to the increased solubility in the mobile phase and reduced affinity for the additive-modified surfactant-coated stationary phase. The comparison of the elution strength of micellar mobile phases with that of a reference acetonitrile-water system indicates that the elution strength is lower for micellar systems and depends on the nature of the eluted solute. The displacement of the solute-micelle and solute-stationary phase binding equilibria is quantified for several probe solutes eluted with micellar mobile phases in the presence of 1-propanol, 1-butanol, 1-pentanol, and acetonitrile. A correlation was also observed between the number of theoretical plates and the hydrophobicity of the alcohol additives: the efficiency initially increased steeply and reached a plateau. Compared to benzene, a more hydrophobic additive was needed to attain the maximum efficiency for the more hydrophobic 2-ethylanthraquinone analyte. Dipolar aprotic solvents appear to be somewhat more effective in enhancing the efficiency than alcohols. The results are rationalized in terms of the ability of the organic additives to alter the composition, structure, dynamics, and properties of the micelles and the surfactant-coated stationary phase.

Journal Article↗
PubMed2000

Role of the carbohydrate moieties in chiral recognition on teicoplanin-based LC stationary phases.

For this study, we used the macrocyclic antibiotic teicoplanin, a molecule consisting of an aglycone peptide "basket" with three attached carbohydrate (sugar) moieties. The sugar units were removed and the aglycone was purified. Two chiral stationary phases (CSPs) were prepared in a similar way, one with the native teicoplanin molecule and the other with the aglycone. Twenty-six compounds were evaluated on the two CSPs with seven RPLC mobile phases and two polar organic mobile phases. The compounds were 13 amino acids or structurally related compounds (including DOPA, folinic acid, etc.) and 13 other compounds (such as carnitine, bromacil, etc.). The chromatographic results are given as the retention, selectivity, and resolution factors along with the peak efficiency and the enantioselective free energy difference corresponding to the separation of the two enantiomers. The polarities of the two CSPs are similar. It is clearly established that the aglycone is responsible for the enantioseparation of amino acids. The difference in enantioselective free energy between the aglycone CSP and the teicoplanin CSP was between 0.3 and 1 kcal/mol for amino acid enantioseparations. This produced resolution factors 2-5 times higher with the aglycone CSP. Four non amino acid compounds were separated only on the teicoplanin CSP. Six and five compounds were better separated on the teicoplanin and aglycone CSPs, respectively. Although the sugar units decrease the resolution of alpha-amino acid enantiomers, they can contribute significantly to the resolution of a number of non amino acid enantiomeric pairs.

Anti-Bacterial Agents↗
PubMed1999

Plant and soil enantioselective biodegradation of racemic phenoxyalkanoic herbicides.

The biodegradation of the chiral phenoxyalkanoic herbicides 2-(2,4-dichlorophenoxy)propionic aid (2,4-DP) and 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) was investigated using enantioselective HPLC and chiroptical detection. Racemic mixtures of 2,4-DP and MCPP were applied to three species of turf grass, four species of broadleaf weeds, and soil. Preferential degradation of the S-(-) enantiomer of each herbicide was observed in most species of broadleaf weeds and soil, while the degradation in all species of grass occurred without enantioselectivity. The biodegradation in all systems appeared to follow pseudo first-order kinetics with the fastest degradation occurring in broadleaf weeds, followed by the grasses. The slowest degradation was observed in soil. The results of this work illustrate the need to characterize both enantiomers of chiral agrochemicals in order to have an accurate understanding of their distribution and fate in the environment.

2,4-Dichlorophenoxyacetic Acid↗