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Joe P Foley

Publications and source records attributed to Joe P Foley.

At least 19 recordsLinked to original sources

Size-exclusion chromatography using deuterated mobile phases.

The effect of deuterated solvents in size-exclusion chromatography (SEC) was studied by comparing intrinsic viscosity measurements, SEC calibration curves, and column efficiency using water-soluble polymers. For aqueous SEC, the use of deuterium oxide slightly increases the SEC elution volume. To verify that adsorption onto the packing was absent, data from exclusion experiments were compared at 35 and 50 degrees C. Our results indicate that adsorption is not occurring for pullulan or polyethylene glycol (PEG)/poly(ethylene oxide) (PEO); for the latter, however, the elution volume increased using both D2O and H2O, indicative of slight hydrodynamic volume contraction of PEG/PEO at higher temperatures. A moderate increase in band broadening (moderate decrease in column efficiency) was observed using D2O. Finally, the effects of chloroform versus deuterated chloroform were evaluated, but no hydrodynamic volume changes were observed.

Adsorption↗

Quantitative theory of electroosmotic flow in fused-silica capillaries using an extended site-dissociation--site-binding model.

To optimize separations in capillary electrophoresis, it is important to control the electroosmotic mobility of the running buffer and the factors that affect it. Through the application of a site-dissociation-site-binding model, we demonstrated that the electroosmotic mobility could be controlled qualitatively and quantitatively by the parameters related to the physical and chemical properties of the running buffer: pH, cation valence, ionic strength, viscosity, activity, and dissociation constant. Our study illustrated that the logarithm of the number of apparent silanol sites on a fused-silica surface has a linear relationship with the pH of a buffer solution. The extension of the chemical kinetics approach allowed us to obtain the thickness of the electrical double layer when multivalent inorganic cations are present with monovalent cations in a buffer solution, and we found that the thickness of the electrical double layer does not depend on the charge of anions. The general equation to predict the electroosmotic mobility suggested here also indicates the increase of electroosmotic mobility with temperature. The general equation was experimentally verified by three buffer scenarios: (i) buffers containing only monovalent cations; (ii) buffers containing multivalent inorganic cations; and (iii) buffers containing cations and neutral additives. The general equation can explain the experimental observations of (i) a maximum electroosmotic mobility for the first scenario as the pH was varied at constant ionic strength and (ii) the inversion and maximum value of the electroosmotic mobility for the second scenario when the concentration of divalent cations was varied at constant pH. A good agreement between theory and experiment was obtained for each scenario.

Binding Sites↗

Chiral microemulsion electrokinetic chromatography with two chiral components: Improved separations via synergies between a chiral surfactant and a chiral cosurfactant.

In this study, the combination of two chiral components in a microemulsion formulation for the separation of enantiomers via microemulsion EKC (MEEKC) was successfully accomplished. Previous publications of chiral microemulsions have utilized only one chiral entity; the surfactant, cosurfactant, or oil was chiral. This is the first study, to date, of the effects of using two chiral species in a single pseudostationary phase (PSP). The chiral surfactant dodecoxycarbonylvaline (DDCV) was used in conjunction with the chiral cosurfactant S-2-hexanol. Ethyl acetate was incorporated as the oil core of the microemulsion and the buffer was 50 mM phosphate at a pH of 7. Additionally, a microemulsion prepared with racemic 2-hexanol was used for comparison to a previous DDCV microemulsion and as a baseline for the newly formulated dual chiral microemulsion. The efficiencies, resolutions, and enantioselectivities for the S-2-hexanol, racemic 2-hexanol, and original 1-butanol DDCV microemulsions are compared. The hexanol-based PSPs provide improved efficiencies and resolutions. To evaluate the combination of each DDCV enantiomer (R and S) with S-2-hexanol, changes in Gibb's free energy were calculated. A synergistic effect was found when two chiral components were combined to form a microemulsion.

1-Butanol↗

Investigation of vesicle electrokinetic chromatography as an in vitro assay for the estimation of intestinal permeability of pharmaceutical drug candidates.

As the pharmaceutical industry continues the daunting search for novel drug candidates, there remains a need for rapid screening methods not only for biological activity, but for physiochemical properties as well. It is invaluable that adequate model systems for absorption and/or bioavailability be developed early in the drug evaluation process to avoid the loss of promising compounds late in development. The focus of this paper is the use of vesicle EKC (VEKC) as a high-throughput, easy, cost-effective, and predictive model for the passive transcellular diffusion of drug candidates in the intestinal epithelium. Vesicles are large aggregates of molecules containing a spherical bilayer structure encapsulating an internal cavity of solvent. It is this bilayer structure that makes vesicles attractive as model membranes. In this study, vesicles were synthesized from both phospholipids and surfactant aggregates, and then employed as pseudostationary phases in EKC (VEKC). The interaction of drug molecules with vesicles in EKC was then used as the basis for an in vitro assay to evaluate passive diffusion. The VEKC technique showed a statistical correlation between the retention of drug candidates using surfactant and phospholipid vesicles and passive diffusion data (log Pow and colon adenocarcinoma). VEKC analysis offers high-throughput capabilities due to the short run times, low sample, and solvent volumes necessary, as well as instrument automation. However, due to the complexity of drug absorption in the intestine, difficulty arises when a single in vitro model is used to predict in vivo absorption characteristics. Therefore, the retention of drug candidates using VEKC in conjunction with other permeability prediction methods can provide a primary screen for a large number of drug candidates early in the drug discovery process with minimal resources.

Biological Transport↗

Chiral microemulsion electrokinetic chromatography: Effect of cosurfactant identity on enantioselectivity, methylene selectivity, resolution, and other chromatographic figures of merit.

The effect of cosurfactant identity on microemulsion size, elution range, retention factor, enantioselectivity, methylene selectivity, efficiency, and resolution in chiral microemulsion formulations was examined. The chiral surfactant dodecoxycarbonylvaline was used in conjunction with the cosurfactants 1-butanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, cyclopentanol, and cyclohexanol. The millimolar concentration of cosurfactant was held constant regardless of identity. Ethyl acetate was incorporated as the microemulsion oil core and the buffer utilized was 50 mM phosphate at a pH of 7.0. In general, secondary alcohols improved enantioselectivities and primary alcohols had the opposite effect, with the exception of the 1-butanol. The trends observed varied slightly depending on analyte. Of the six chiral analytes tested, cyclopentanol provided the best enantioselectivity for three, 1-butanol for two compounds, and 2-pentanol for one analyte. The lowest enantioselectivities were achieved with 1-pentanol or 1-hexanol for all compounds. Methylene selectivity was found to decrease with reductions in alcohol chain length. Among equal carbon number alcohols, methylene selectivity was lower for secondary alcohols. Efficiency and resolution values varied with different cosurfactants and depended on analyte identity.

Acetates↗

Temperature effects on chiral microemulsion electrokinetic chromatography employing the chiral surfactant dodecoxycarbonylvaline.

Dodecoxycarbonylvaline (DDCV) microemulsions (1% and 4%, w/v) were employed to evaluate the retention mechanism of a series of enantiomers over a temperature range of 15-35 degrees C. From the acquired retention data, van't Hoff plots were constructed and enthalpy and entropy of transfer were calculated from the slope and intercept, respectively. Resolution, enantioselectivity, distribution coefficients and Gibb's free energy were also calculated, as well as between enantiomer differences in enthalpy, entropy and Gibb's free energy. Finally, comparisons were made between the microemulsion thermodynamic data and a corresponding set of micellar data. While the 4% DDCV microemulsion did not provide a linear van't Hoff relationship, the 1% DDCV microemulsion was linear over a temperature range of 15-30 degrees C. For the 1% DDCV microemulsion, the enthalpic contribution to retention was consistently favorable (deltaH < 0), whereas the entropic contribution varied from compound to compound. Finally, while the achiral attraction of the analytes was greater for the micellar phase, the microemulsion seemed to provide a suitable difference in entropy (and Gibb's free energy) between enantiomers to achieve chiral discrimination.

Chromatography, Micellar Electrokinetic Capillary↗

Comparison of dodecoxycarbonylvaline microemulsion, solvent-modified micellar and micellar pseudostationary phases for the chiral analysis of pharmaceutical compounds.

A direct comparison of dodecoxycarbonylvaline (DDCV) microemulsion, micellar and butanol-modified micellar aggregate systems was performed employing both 2 and 4% DDCV. With respect to either DDCV concentration, use of the micellar system provided the largest elution range, followed by the butanol-modified micellar system and ultimately the microemulsion. Using 2% DDCV, all three aggregate analyses yielded similar values for enantioselectivity, resolution and retention factors that were slightly better using the micellar phase, but efficiencies were consistently better using either the microemulsion or butanol-modified micellar phases. Largely, the microemulsion and butanol-modified micellar phases behaved fairly similar, although use of the butanol-modified micelle provided resolution and efficiency that were slightly better for all but two of the compounds. While reasonable separations were achieved using 2% DDCV, the results using 4% DDCV for the microemulsion system were far superior. Analyses using analogous micellar and butanol-modified micellar aggregates were unstable, making them unsuitable for use at that surfactant concentration.

Chromatography, Micellar Electrokinetic Capillary↗

Effect of surfactant counterion and organic modifier on the properties of surfactant vesicles in electrokinetic chromatography.

Counterion and organic modifier are two parameters in EKC that can be varied in order to obtain improved solubility, selectivity, and efficiency. The effect of changing surfactant counterion and/or organic modifier on the chromatographic and electrophoretic properties of cetyltrimethylammonium bromide (CTAB)/sodium octyl sulfate (SOS) vesicles is examined in EKC. The vesicles are prepared in a 1:3.66 cationic/ anionic mole ratio for a total surfactant concentration of 69 mM. The cationic CTAB is replaced by cetyltrimethylammonium chloride (CTAC) and the first use of CTAC/SOS vesicles is reported. The mean diameter of the CTAC/SOS vesicles is 96 nm while that of the CTAB/SOS vesicles is 85 nm. A class I modifier (2-amino-1-butanol) and a class II modifier (acetonitrile) have similar effects on the EOF, elution range, methylene selectivity, and the efficiency of the CTAB/SOS vesicles and the CTAC/SOS vesicles. Upon addition of 10% ACN, there is roughly a 10-fold increase in the efficiency of heptanophenone, a model hydrophobic compound, compared to the efficiency using unmodified vesicles. Linear free energy relationship (LFER) analysis using the Abraham solvation model is employed to characterize solute-vesicle interactions. The results suggest that organic modifier-vesicle interactions depend somewhat on the counterion.

Journal Article↗

Stationary-phase effects on efficiency in micellar liquid chromatography.

One of the main limitations of micellar liquid chromatography (MLC) is the lower efficiency compared to reversed-phase liquid chromatography (RPLC) with hydro-organic mobile phases. The main contribution to the reduced efficiency has been shown to be due to the slow mass transfer between micelles, the aqueous phase, and the stationary phase mainly due to surfactant adsorption onto the stationary phase. The use of a variety of stationary phases, including large-pore short alkyl chain, non-porous, superficially porous, and perfluorinated, is shown to have differing effects on remediation of the reduced efficiency. Diffusion coefficients were determined by the Taylor-Aris dispersion technique for the construction of Knox plots. The Knox plots are used to compare the efficiency data obtained with the different columns using several alkylphenones in both micellar mobile phase and hydro-organic mobile phase.

Chromatography, Liquid↗

Analytical method for the quantitation of sertraline hydrochloride stereoisomers by electrokinetic chromatography.

Sertraline is a basic compound and of pharmaceutical application for antidepressant treatment. The compound has two chiral centers. Separation of the three enantiomeric impurities from the parent compound is challenging. In this study, we successfully separated all four stereoisomers by electrokinetic chromatography using highly sulfated gamma-cyclodextrin and highly sulfated alpha-cyclodextrin as the chiral selectors. The two chiral selectors provided different selectivity and therefore affected the overall separation profiles. This may be due to the size difference between the dichlorophenyl moiety end and naphthalenamine moiety end, resulting in two different types of inclusion complexes with the different cyclodextrins. For routine analysis, highly sulfated gamma-cyclodextrin was better than highly sulfated alpha-cyclodextrin. For each stereoisomeric impurity, the method using sulfated gamma-cyclodextrin provided a limit of quantitation at or lower than 0.1% of the drug substance with adequate resolution. The critical resolution at this concentration level was not less than 4.0. Experimental data suggested that an internal standard was necessary for the purpose of quantitation, and the practical linearity range for analysis of sertraline stereoisomeric impurities was of about two orders of magnitude.

Chromatography, Micellar Electrokinetic Capillary↗

Effect of oil substitution in chiral microemulsion electrokinetic chromatography.

In a previous publication (Pascoe, R., Foley, J. P., Analyst 2002, 127, 710-714), a novel chiral microemulsion based on 1.0% w/v dodecoxycarbonylvaline (DDCV), 0.50% v/v ethyl acetate and 1.2% v/v 1-butanol, was shown to provide rapid enantiomeric separations of various pharmaceutical compounds. The two deficiencies noted with this method were that the peak shapes obtained were asymmetric and the efficiencies were lower than those previously obtained using DDCV micelles (Peterson, A. G., Ahuja, E. S., Foley, J. P., J. Chromatogr. B 1996, 683, 15-28). This study examines the use of three alternative low-interfacial-tension oils (methyl acetate, methyl propionate, and methyl formate), in combination with DDCV, to characterize their effect on the elution range, efficiency, resolution, and enantioselectivity of various pharmaceutical enantiomers. The oils were evaluated in both the same volume percentage and the same molar concentration as ethyl acetate in the original DDCV microemulsion system. Including ethyl acetate, a total of seven microemulsion systems were examined. For the compounds that were separated, average enantioselectivities ranged from 1.09 to 1.28, with corresponding efficiencies of 14,000-20,000. While some interesting differences were observed, ethyl acetate still proved to be the most advantageous in terms of enantioselectivity, resolution, and elution range.

Acetates↗

Dual opposite injection electrokinetic chromatography: nonionic microemulsion pseudostationary phase and novel approach to electrokinetic sampling bias.

Dual opposite injection capillary electrophoresis (DOI-CE) is a family of CE techniques in which the sample is introduced into both ends of the capillary. For the analysis of compounds with widely varying pKa values using a voltage-driven separation scheme, DOI-CE is superior to conventional CE with sample introduction at only one end of the capillary due to DOI-CE's broader elution window. To enhance the DOI-CE separation, a running buffer with a microemulsion system was developed. Since DOI-CE works best under conditions of low electroosmotic flow (EOF), the suppression of EOF via the addition of a multiply charged cation (e.g., Zn2+) to the buffer was investigated, and was found to suppress the EOF effectively at moderate concentrations (2.5-10 mM). Three different dual opposite injection modes were studied: simultaneous electrokinetic injection, sequential electrokinetic injection, and sequential hydrodynamic injection. The injection bias in the first two electrokinetic injection modes was compared with the sequential hydrodynamic injection. Corrections in the bias of the electrokinetic injections were discussed, and an improved approach was suggested. Finally, the effect of the relative concentration of the multiply charged cation in the sample plug and running buffer on the peak shape of co-electroosmotic and counter-electroosmotic ions was examined, and found to be much more influential on the latter.

Anions↗

Chiral cyclodextrin-modified microemulsion electrokinetic chromatography.

Cyclodextrin (CD)-modified microemulsion electrokinetic chromatography (MEEKC) or CD-MEEKC has not previously been applied to the area of chiral separations. Herein, the results of investigations of various microemulsions with CD additives are presented. Two different microemulsions are explored: an ethyl acetate sodium dodecyl sulfate microemulsion, and a chiral dodecoxycarbonylvaline (DDCV) microemulsion. Each microemulsion is paired separately with a neutral CD (hydroxypropyl-beta-CD) and an anionic CD (sulfated-beta-CD). In addition, the chiral DDCV microemulsion is investigated in both the R- and S- form. By varying simple parameters such as buffer system, applied voltage, surfactant enantiomer, and type of cyclodextrin, dramatic improvements in the chiral separations were noted. Resolution was found to be highly dependent on buffer identity and concentration, and somewhat dependent on whether the CDs used were randomly or highly sulfated. Under optimized conditions, the resolution ranged from 0.8 to 4.8, with plate counts ranging from 4000 to 26 000. Additionally, S- and R-levetiracetam, which had never before been enantioseparated via capillary electrophoresis (CE) methodologies, were separated in less than 8 min, with a resolution of 1.1.

Buffers↗

Effect of surfactant concentration and buffer selection on chromatographic figures of merit in chiral microemulsion electrokinetic chromatography.

The enantiomeric resolution of 15 different pharmaceutical compounds was explored using chiral microemulsion electrokinetic chromatography (MEEKC). The microemulsion employed was comprised of the chiral surfactant dodecoxycarbonylvaline (DDCV), 1-butanol, and ethyl acetate, at an initial composition of 1% w/v:1.2% v/v:0.5% v/v, respectively. The effect of varying the background buffer composition, voltage, and ultimately the surfactant concentration and/or aggregate phase ratio were examined. Changing from a zwitterionic buffer ((2-[2-amino-2-oxoethyl)amino]ethanesulfonic acid, ACES) to the same concentration of phosphate buffer improved the efficiency and decreased overall analysis time, but also resulted in a decrease in chiral resolution. Furthermore, using phosphate buffer while simultaneously increasing the percent DDCV from 1 to 4% increased the efficiencies from a range of 34,000 to 59,000 N/m to a range of 160,000 to 400,000 N/m. While the enantioselectivities did not change significantly, the improvement in efficiencies, elution range, and retention factors provided an increase in both resolution and the number of enantiomers that were separated. Using an optimized microemulsion comprised of phosphate buffer and 4% DDCV, chiral separation was achieved for all 11 pairs of enantiomers, with a resolution ranging from 0.90 to 4.71. Moreover, the average resolution doubled in going from nonoptimized to optimized conditions for five of the eleven compounds. Finally, a comparison was made of the effect of increasing only the surfactant concentration by a factor of 4 versus increasing the overall composition (or phase ratio) by a factor of 4. Ultimately, the microemulsion containing 4% DDCV provided a larger elution range, greater resolution, and more optimal retention than that provided by the 4x phase increase.

Buffers↗

Chromatographic performance of large-pore versus small-pore columns in micellar liquid chromatography.

Micellar liquid chromatography (MLC) is useful in bioanalysis because proteinaceous biofluids can be directly injected onto the column. The technique has been limited in part because of the apparently weak eluting power of micellar mobile phases. It has recently been shown [Anal. Chem. 72 (2000) 294] that this may be overcome by the use of large pore size stationary phases. In this work, large-pore (1000 A) C(18) stationary phases were evaluated relative to conventional small-pore (100 A) C(18) stationary phases for the direct sample injection of drugs in plasma. Furthermore, the difference between the large and small pore phases in gradient elution separations of mixtures of widely varying hydrophobicities was investigated. Large-pore stationary phases were found to be very effective for eluting moderately to highly hydrophobic compounds such as ibuprofen, crotamiton, propranolol, and dodecanophenone, which were highly retained on the small-pore stationary phases typically used in MLC. The advantages of direct introduction of biological samples (drugs in plasma) and rapid column re-equilibration after gradient elution in MLC were maintained with large-pore phases. Finally, recoveries, precision, linearity, and detection limits for the determination of quinidine and DPC 961 in spiked bovine plasma were somewhat better using MLC with wide pore phases.

Chromatography, Liquid↗

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.

Chromatography, Micellar Electrokinetic Capillary↗

Effect of class I and II organic modifiers on retention and selectivity in vesicle electrokinetic chromatography.

Vesicles are large aggregates of surfactant monomers consisting of a spherical bilayer surrounding an internal cavity of solvent. The bilayer structure allows vesicles to be attractive models for the study of various transmembrane and binding processes. The use of thermodynamically stable vesicles (TSV) formed from oppositely charged surfactants for use as a pseudostationary phase in electrokinetic chromatography (EKC) was first accomplished using dodecyltrimethylammonium bromide and sodium dodecyl sulfate (DTAB/SDS). Surfactant vesicles have demonstrated enhanced separation characteristics compared to conventional micelles in EKC, although only investigated in aqueous media. Organic modifiers have been widely studied and used in EKC to enhance separation conditions. In this study, vesicles formed from cetyltrimethylammonium bromide and sodium octyl sulfate (CTAB/SOS) were investigated in the presence of "class I and II" organic modifiers. Electrophoretic and chromatographic parameters were examined as well as linear solvation energy relationship analysis (LSER) to characterize the effects of the modifiers on retention and selectivity in EKC. LSER analysis is a useful way to quantitatively investigate solute/solvent interactions responsible for retention and selectivity.

Chromatography, Micellar Electrokinetic Capillary↗

Rapid separation of pharmaceutical enantiomers using electrokinetic chromatography with a novel chiral microemulsion.

A novel oil-in-water microemulsion incorporating the chiral surfactant dodecoxycarbonylvaline (DDCV) was used to achieve the rapid enantiomeric separation of pharmaceutical drugs by electrokinetic chromatography (EKC). Incorporation of DDCV into a microemulsion resulted in an elution range more than double that provided the micellar form of the surfactant aggregate. Interestingly, for the same compounds the enantioselectivity provided by the chiral DDCV microemulsions ranged from 1.06-1.30 for the neutral and cationic drugs, which was slightly higher than that provided by chiral DDCV micelles. The use of a low surface tension oil (ethyl acetate) permitted a much lower concentration of chiral surfactant to be employed; this, together with the use of a zwitterionic buffer (ACES) resulted in a very low conductivity microemulsion that allowed a higher separation voltage to be utilized, resulting in rapid enantiomeric separations (< 8 min.). Mobility matching of the buffer cation(s) was used to improve peak shape and efficiencies. In our limited survey of the phase diagram, the optimum composition of the microemulsion buffer was 1.0% (w/v) DDCV (30 mM), 0.5% (v/v) ethyl acetate, 1.2% (v/v) 1-butanol and 50 mM ACES buffer at pH 7.

Chromatography, Micellar Electrokinetic Capillary↗