Elisabeth Bosch | University of Barcelona (original) (raw)

Papers by Elisabeth Bosch

This chapter reviews the most important features of the buffers commonly employed in capillary el... more This chapter reviews the most important features of the buffers commonly employed in capillary electrophoresis. Effect of the buffer properties such as pH, concentration, or ionic strength, on the electro-osmotic flow and on acid–base analytes migration is discussed. Other parameters that can affect buffer properties or analyte migration during CE separations, such as temperature, electrolysis time, or buffer-analyte interactions, are also reviewed.

Journal of Physical Organic Chemistry, Mar 1, 1998

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Analytical Chemistry, Jan 15, 1990

The progressive addition of cosolvent into any particular solution of an electrolyte causes a gra... more The progressive addition of cosolvent into any particular solution of an electrolyte causes a gradual change in the dissociation constant (pK) of the electrolyte. The changes in pK values of picric acid and tetrabutylammonium picrate in isopropyl alcohol-cosolvent mixtures have been related with the dielectric constant (e) and the polarity of the mixed solvent, the latter measured by means of Dimroth-Reichardt's parameter. Theoretical equations, which show linear relationships between these magnitudes and also with the solvent composition, have been developed. A variety of cosolvents of different polarity have been used

Butlletí de les Societats Catalanes de Física, Química, Matemàtiques i Tecnologia, 1987

This paper is a contribution to assess the present state of chemical and chromatic studies of che... more This paper is a contribution to assess the present state of chemical and chromatic studies of chemical indicators both in aqueous and the main non-aqueous solvents. It deals with the theoretical approach and practical procedure to characterize the transition ranges, pH of maximum colour change, optimum concentration for the titration and quality of colour change, as well as the determination of pKa values. Equations defining the transition straight line in complementary chromaticity diagram and conditions defining the best screened indicator to be prepared from a given pure acid-base indicator and dyes are also given.

Revista De Educacion, 1984

... Como resultado, se destacan las dificultades con que se encuentra un profesor al inicio de su... more ... Como resultado, se destacan las dificultades con que se encuentra un profesor al inicio de su carrera en cuanto al contenido de la materia que han de impartir, y en cuanto a la vertiente pedagógica de su labor. Details der Publikation. ...

European Journal of Pharmaceutical Sciences, 2022

A wide set of well-known drugs, most of them included in the Abraham´s reference database, coveri... more A wide set of well-known drugs, most of them included in the Abraham´s reference database, covering a wide variety of chemical structures and therapeutical functionalities were chosen in order to determine some molecular properties from solvent/water partition measurements. Partition data from aqueous solutions and four different solvents (n-dodecane, toluene, chloroform and n-octanol) were measured and reported. From them, Abraham´s molecular descriptors of selected compounds (A, B and S, accounting for hydrogen bond donor, hydrogen bond acceptor and dipolarity/polaritzability, respectively) were estimated. A and B values derived from the experimental measurements strongly agree with the tabulated ones showing the suitability of the used procedure to achieve reliable values for new molecules. However, obtained S values differ from those previously reported for several compounds. Moreover, values for a new indicator of the propensity to form intramolecular hydrogen bonds (Δlog Poct-tol) were estimated from the experimental data and also calculated according to both, the Abraham´s model and the molecular structures (SMD). The quality of both series of calculated descriptors was evaluated by contrast with the experimental values and satisfactory results were obtained in both instances. Thus, the Abraham´s way is useful when molecular descriptors are available but very good estimations can be achieved by SMD, which only requires the drug´s molecular structure.

Journal of Chromatography A, 2001

Several micellar electrokinetic chromatography (MEKC) systems (sodium dodecyl sulfate, lithium do... more Several micellar electrokinetic chromatography (MEKC) systems (sodium dodecyl sulfate, lithium dodecyl sulfate, lithium perfluorooctanesulfonate, sodium cholate, sodium deoxycholate, tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide) have been characterized by means of the solvation parameter model. It has been observed that the coefficients of the correlation equations depend strongly on the particular set of compounds analyzed. Principal component analysis has been used to

Journal of Chromatography A, Apr 1, 2009

A set of 25 monoprotic bases is proposed as internal standards for pK a determination by capillar... more A set of 25 monoprotic bases is proposed as internal standards for pK a determination by capillary electrophoresis. The pK a of the bases is determined and compared with available literature data. The capillary electrophoresis internal standard method offers numerous advantages over other typical methods for pK a determination, especially of analysis time and buffer preparation. However, it requires disposing of appropriate standards with reference pK a value. The set of bases established in this work together with the set of acids previously established provide a reference set of compounds with well-determined acidity constants that facilitate the process of selecting appropriate internal standards for fast pK a determination by capillary electrophoresis in high throughput screening of pharmaceutical drugs. In addition, the performance of the method when acidic internal standards are used for the determination of acidity constants of basic internal standards has also been tested. Although higher errors may be expected in this case, good agreement is observed between determined and literature values. These results indicate that in most cases structural similarity between the analyte and the internal standard might not be an essential requirement in the internal standard method.

Journal of the Chemical Society, 1995

ABSTRACT

Journal of Chemical Education, Jun 1, 1990

Journal of Chromatography A, Jun 1, 1999

The solvation parameter model has been applied to the characterization of micellar electrokinetic... more The solvation parameter model has been applied to the characterization of micellar electrokinetic chromatographic (MEKC) systems with mixtures of sodium dodecyl sulfate and Brij 35 as surfactant. The variation in MEKC surfactant composition results in changes in the coefficients of the correlation equation, which in turns leads to information on solute–solvent and solute–micelle interactions. Since the same solvation model can

Molecular Pharmaceutics, May 13, 2021

It is widely accepted that solubility-pH profiles of ionizable compounds follow the Henderson-Has... more It is widely accepted that solubility-pH profiles of ionizable compounds follow the Henderson-Hasselbalch equation. However, several studies point out that compounds often undergo additional processes in saturated solutions, such as sub-micellar oligomerization, micellar aggregation, or drug-buffer complexation among others, which make the experimental profiles deviate from the behavior predicted by Henderson-Hasselbalch equation. Often, the presence of additional processes is supported by the analysis of experimental data through solubility computer programs. However, the purpose of this work is to experimentally prove the aggregation phenomena for a series of bases for which deviations to the theoretical profile have been observed. To this end, five monoprotic bases (lidocaine, maprotiline, cyproheptadine, bupivacaine, and mifepristone) susceptible to form ionic aggregates in solution have been selected, and mass spectrometry has been the technique of choice to prove the presence of aggregation. High declustering potentials have been applied to prevent aggregates from forming in the ionization source of the mass spectrometer. In addition, haloperidol has been used as negative control, since according to its profile it is not suspected to form ionic aggregates. In all instances, except for haloperidol, the analysis of the saturated solutions revealed the presence of mixed charged dimers (aggregates formed by a neutral molecule and a charged one) and even trimers in case of mifepristone and bupivacaine. For lidocaine, the most soluble of the compounds, the presence of neutral aggregates was also detected. These experiments support the hypothesis that the simple Henderson-Hasselbalch equation may explain the solubility-pH behavior of certain compounds, but it can be somewhat inaccurate in describing the behavior of many other substances.

Journal of Separation Science, Apr 1, 2008

We propose a general simple equation for accurately predicting the retention factors of ionizable... more We propose a general simple equation for accurately predicting the retention factors of ionizable compounds upon simultaneous changes in mobile phase pH and column temperature at a given hydroorganic solvent composition. Only four independent experiments provide the input data: retention factors measured in two pH buffered mobile phases at extreme acidic and basic pH values (e. g., at least l 2 pH units far from the analyte pK a) and at two column temperatures. The equations, derived from the basic thermodynamics of the acid-base equilibria, additionally require the knowledge of the solute pK a and enthalpies of acid-base dissociation of both the solute and the buffer components in the hydroorganic solvent mixture. The performance of the predictive model is corroborated with the comparison between theoretical and experimental retention factors of several weak acids and bases of important pharmacological activity, in mobile phases containing different buffer solutions prepared in 25% w/w ACN in water and at several temperatures.

Journal of Physical Organic Chemistry, Mar 1, 1998

ABSTRACT

Analytica Chimica Acta, Aug 1, 1997

The autoprotolysis of binary aqueous mixtures of dimethyl sulfoxide, acetonitrile, acetone, tetra... more The autoprotolysis of binary aqueous mixtures of dimethyl sulfoxide, acetonitrile, acetone, tetrahydrofuran and 1,4-dioxan is studied. It is demonstrated that except for solvent mixtures very rich in water, the autoprotolysis is produced by proton transfer from water to the dipolar organic solvent. Only in water rich mixtures the autoionization of water contributes appreciably to autoprotolysis. It is also suggested that

Talanta, Dec 1, 1989

The dissociation constants of several families of acids (substituted phenols and mercaptopyrimidi... more The dissociation constants of several families of acids (substituted phenols and mercaptopyrimidines) in isopropyl alcohol medium have been determined by potentiometric titration with tetrabutylammonium hydroxide. Because of ion-pair formation the incomplete dissociation of the tetrabutylammonium salt has been taken into account in the calculation of pK(a). The dissociation constants of the salts were previously measured conductometrically. The resolution of acid strength in isopropyl alcohol relative to that in water has been determined for each series of acids by plotting the pK(a) values in isopropyl alcohol vs. those in water. The results show greater resolution in isopropyl alcohol than in water. The resolution of acid strength in tert-butyl alcohol relative to that in isopropyl alcohol has also been determined.

Talanta, Jun 1, 1989

Analytical Chemistry, Sep 1, 1993

... Acta 1993,276, 211-221. (8) Rosbs, M. Anal. Chim. Acta 1993,276, 223-234. (9) Mob, C.; ROB&am... more ... Acta 1993,276, 211-221. (8) Rosbs, M. Anal. Chim. Acta 1993,276, 223-234. (9) Mob, C.; ROB&, M.; Bosch, E. Anal. Chim. Acta 1993,280,75-83. ... 422. (20) Longhi, P.; Mussini,T.; Veleva, MG Anal.Quim. 1975,71,1043-(21) Georgieva, M.; Velinov, G.; Budevsky, 0. Anal. Chim. ...

Journal of Chromatography A, Jul 1, 2004

The retentive behavior of weak acids and bases in reversed-phase liquid chromatography (RPLC) upo... more The retentive behavior of weak acids and bases in reversed-phase liquid chromatography (RPLC) upon changes in column temperature has been theoretically and experimentally studied. The study focuses on examining the temperature dependence of the retention of various solutes at eluent pH close to their corresponding pK a values, and on the indirect role exerted by the buffer ionization equilibria on retention and selectivity. Retention factors of several ionizable compounds in a typical octadecylsilica column and using buffer solutions dissolved in 30% (v/v) acetonitrile as eluent at five temperatures in the range from 25 to 50 • C were carefully measured. Six buffer solutions were prepared from judiciously chosen conjugated pairs of different chemical nature. Their pK a values in this acetonitrile-water composition and within the range of 15-50 • C were determined potentiometrically. These compounds exhibit very different standard ionization enthalpies within this temperature range. Thus, whenever they are used to control mobile phase pH, the column temperature determines their final pH. Predictive equations of retention that take into account the temperature effect on both the transfer and the ionization processes are evaluated. This study demonstrates the significant role that the selected buffer would have on retention and selectivity in RPLC at temperatures higher than 25 • C, particularly for solutes that coelute.

Journal of Physical Organic Chemistry, Mar 1, 1998

ABSTRACT

Analytical Chemistry, Jan 15, 1990

Butlletí de les Societats Catalanes de Física, Química, Matemàtiques i Tecnologia, 1987

Revista De Educacion, 1984

European Journal of Pharmaceutical Sciences, 2022

Journal of Chromatography A, 2001

Journal of Chromatography A, Apr 1, 2009

Journal of the Chemical Society, 1995

ABSTRACT

Journal of Chemical Education, Jun 1, 1990

Journal of Chromatography A, Jun 1, 1999

Molecular Pharmaceutics, May 13, 2021

Journal of Separation Science, Apr 1, 2008

Journal of Physical Organic Chemistry, Mar 1, 1998

ABSTRACT

Analytica Chimica Acta, Aug 1, 1997

Talanta, Dec 1, 1989

Talanta, Jun 1, 1989

Analytical Chemistry, Sep 1, 1993

Journal of Chromatography A, Jul 1, 2004

Cromatografía y Técnicas Afines, 2009

Es bien sabido que el pH de la fase móvil es una variable fundamental en la separación de sustanc... more Es bien sabido que el pH de la fase móvil es una variable fundamental en la separación de sustancias ionizables en cromatografía de líquidos, ya que de él depende el grado de ionización de los analitos presentes en la mezcla problema. En el desarrollo de métodos analíticos se requiere pues, ejercer un control eficiente sobre el pH mediante la elección de un tampón adecuado. En cromatografía de líquidos en fase inversa, suelen usarse soluciones hidro-orgánicas tamponadas como fases móviles. Habitualmente éstas suelen prepararse añadiendo el volumen adecuado de un disolvente orgánico, típicamente acetonitrilo o metanol, sobre una solución acuosa tamponada. Sin embargo, fases móviles del mismo contenido en modificador orgánico y preparadas a partir de soluciones acuosas del mismo pH pero que contienen ácidos distintos como reguladores del pH, pueden presentar valores de pH significativamente diferentes. Consideremos el ejemplo mostrado en la Figura 1. Se inyectó una mezcla de sustancias con propiedades ácido-base, de pK a cercano a 8, en dos fases móviles distintas que contenían un 60% de acetonitrilo. Ambas fases móviles se prepararon añadiendo el volumen adecuado de acetonitrilo a soluciones acuosas tamponadas del mismo pH (8,00), pero preparadas a partir de distintas especies reguladoras del pH: y . Podemos observar en la Figura 1 que los tiempos de retención para dos de los cuatro analitos son significativamente distintos y, en función del tampón utilizado, se obtienen diferentes perfiles de elución. Este fenómeno también se produce en fases móviles que contengan metanol como modificador orgánico, tal y como se desprende de los cromatogramas mostrados en la Figura 2. ¿Cuál es el motivo del cambio de selectividad en los ejemplos descritos? La respuesta la encontraremos al final del artículo, pero antes de llegar a ella deberemos hacer algunas consideraciones prácticas sobre la medida del pH en fases móviles hidro-orgánicas y sobre las variaciones del pK a de ácidos y bases con la adición de modificador orgánico.

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, 2015

The parameters affecting the properties of buffers commonly used in chromatographic mobile phases... more The parameters affecting the properties of buffers commonly used in chromatographic mobile phases, mainly the content of organic solvent and temperature, are examined. They play a key role in the pH of maximum buffer capacity and the effective pH range of buffering action. The effect of organic modifier on the pKa of buffering acids and bases and, consequently, on the pH is discussed, and the relation of this pH variation with the retention of analytes with acid–base properties is pointed out. The different pH scales used in hydroorganic mobile phases and their relationships are discussed as well.

Journal of Chromatography A, 2009

In previous works a model to estimate the pH of methanol–aqueous buffer mobile phases from the aq... more In previous works a model to estimate the pH of methanol–aqueous buffer mobile phases from the aqueous pH and concentration of the buffer and the fraction of organic modifier was developed. This model was successfully applied and validated for buffers prepared from ammonia, acetic, phosphoric and citric acids. In the present communication this model has been extended to formic acid, piperazine and tris(hydroxymethyl)aminomethane buffers. Prior to the modelling work, the pKa values of the studied buffers at several methanol–water compositions were determined.

Journal of Chromatography A, 2009

In the present work dissociation constants of commonly used buffering species, formic acid, piper... more In the present work dissociation constants of commonly used buffering species, formic acid, piperazine, tris(hydroxymethyl)–aminomethane, boric acid and carbonate, have been determined for several acetonitrile–water mixtures. From these pKa values a previous model has been successfully evaluated to estimate pH values in acetonitrile–aqueous buffer mobile phases from the aqueous pH and concentration of the above mentioned buffers up to 60% of acetonitrile, and aqueous buffer concentrations between 0.005 (0.001 mol L−1 for formic acid–formate) and 0.1 mol L−1. The relationships derived for the presently studied buffers, together with those established for previously considered buffering systems, allow a general prediction of the pH variation of the most commonly used HPLC buffers when the composition of the acetonitrile–water mobile phase changes during the chromatographic process, such as in gradient elution. Thus, they are an interesting tool that can be easily implemented in general retention models to predict retention of acid–base analytes and optimize chromatographic separations.

Journal of Chromatography A, 2009

General models in reversed-phase liquid chromatography that have been extended to relate retentio... more General models in reversed-phase liquid chromatography that have been extended to relate retention of ionizable compounds to mobile phase composition, pH and/or temperature are reviewed. In particular, the fundamentals and applications of the solvation parameter model, the polarity parameter model and several classical models based on empirical equations are presented and compared. A main parameter in all these models is the degree of ionization of the acid–base compound, which depends on both the pH of the mobile phase and the acid–base constant of the compound. Thus, on one hand, the different procedures for pH measurement in the mobile phase and their influence on the performance of the models are outlined. On the other hand, equations that relate the variation of the pH of the buffer and the pKa of the compound with the mobile phase composition and/or temperature are reviewed and their applicability to the retention models critically discussed.

Separation & Purification Reviews, 2007

A review about the analyte pKa and buffer pH variations in RP‐HPLC mobile phases with the changes... more A review about the analyte pKa and buffer pH variations in RP‐HPLC mobile phases with the changes in the organic modifier content (acetonitrile or methanol) is presented. A model to accurately predict the pH of particular mobile phases for several commonly used buffers (acetic, citric and phosphoric acid and ammonia systems) in acetonitrile‐water and methanol‐water mixtures is described. Linear relationships are also presented for several families of acid‐base compounds (aromatic and aliphatic carboxylic acids, phenols, amines and pyridines) to estimate pKa values of analytes in methanol‐water and acetonitrile‐water from their corresponding aqueous pKa. From both, the estimated pH of the mobile phase and the estimated pKa of acid‐base analytes, it is possible to predict their degree of ionization and, therefore, the analyte chromatographic retention.

$Research paper thumbnail of Retention of ionisable compounds on high-performance liquid chromatography XVII: Estimation of the pH variation of aqueous buffers with the change of the methanol fraction of the mobile phase$

Journal of Chromatography A, 2007

The use of methanol–aqueous buffer mobile phases in HPLC is a common election when performing chr... more The use of methanol–aqueous buffer mobile phases in HPLC is a common election when performing chromatographic separations of ionisable analytes. The addition of methanol to the aqueous buffer to prepare such a mobile phase changes the buffer capacity and the pH of the solution. In the present work, the variation of these buffer properties is studied for acetic acid–acetate, phosphoric acid–dihydrogenphosphate–hydrogenphosphate, citric acid–dihydrogencitrate–hydrogencitrate–citrate, and ammonium–ammonia buffers. It is well established that the pH change of the buffers depends on the initial concentration and aqueous pH of the buffer, on the percentage of methanol added, and on the particular buffer used. The proposed equations allow the pH estimation of methanol–water buffered mobile phases up to 80% in volume of organic modifier from initial aqueous buffer pH and buffer concentration (before adding methanol) between 0.001 and 0.01 mol L−1. From both the estimated pH values of the mobile phase and the estimated pKa of the ionisable analytes, it is possible to predict the degree of ionisation of the analytes and therefore, the interpretation of acid–base analytes behaviour in a particular methanol–water buffered mobile phase.

Journal of Chromatography A, 2006

In agreement with our previous studies and those of other authors, it is shown that much better f... more In agreement with our previous studies and those of other authors, it is shown that much better fits of retention time as a function of pH are obtained for acid–base analytes when pH is measured in the mobile phase, than when pH is measured in the aqueous buffer when buffers of different nature are used. However, in some instances it may be more practical to measure the pH in the aqueous buffer before addition of the organic modifier. Thus, an open methodology is presented that allows prediction of chromatographic retention of acid–base analytes from the pH measured in the aqueous buffer. The model presented estimates the pH of the buffer and the pKa of the analyte in a particular acetonitrile/water mobile phase from the pH and pKa values in water. The retention of the analyte can be easily estimated, at a buffer pH close to the solute pKa, from these values and from the retentions of the pure acidic and basic forms of the analyte. Since in many instances, the analyte pKa values in water are not known, the methodology has been also tested by using Internet software, at reach of many chemists, which calculates analyte pKa values from chemical structure. The approach is successfully tested for some pharmaceutical drugs.

$Research paper thumbnail of Retention of ionisable compounds on high-performance liquid chromatography: XV. Estimation of the pH variation of aqueous buffers with the change of the acetonitrile fraction of the mobile phase$

Journal of Chromatography A, 2004

The most commonly used mobile phases in reversed-phase high-performance liquid chromatography (RP... more The most commonly used mobile phases in reversed-phase high-performance liquid chromatography (RP-HPLC) are hydro-organic mixtures of an aqueous buffer and an organic modifier. The addition of this organic solvent to buffered aqueous solutions involves a variation of the buffer properties (pH and buffer capacity). In this paper, the pH variation is studied for acetic acid–acetate, phosphoric acid–dihydrogenphosphate–hydrogenphosphate, citric acid–dihydrogencitrate–citrate, and ammonium–ammonia buffers. The proposed equations allow pH estimation of acetonitrile–water buffered mobile phases up to 60% (v/v) of organic modifier and initial aqueous buffer concentrations between 0.001 and 0.1 mol L−1, from the initial aqueous pH. The estimated pH variation of the mobile phase and the pKa variation of the analytes allow us to predict the degree of ionisation of the analytes and from this and analyte hydrophobicities, to interpret the relative retention and separation of analyte mixtures.

Elsevier European Journal of Pharmaceutical Sciences, 2018

In the present study three different procedures have been compared for the determination of the l... more In the present study three different procedures have been compared for the determination of the lipophilicity of the unionized species (log Po/w) of neutral, acidic, basic, amphoteric, and zwitterionic drugs. Shake-flask, potentiometric and chromatographic approaches have been assayed in a set of 66 representative compounds in different phases of advanced development. An excellent equivalence has been found between log Po/w values obtained by shake-flask and potentiometry, while the chromatographic approach is less accurate but very convenient for screening purposes when a high-throughput is required. In the case of zwitterionic and amphoteric compounds, either for shake-flask and chromatographic methods, the pH has to be accurately selected in order to ensure the compound to be in its neutral form.

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, 2015

Nowadays, pharmaceutical research needs to deal with sparingly soluble compounds and requires hig... more Nowadays, pharmaceutical research needs to deal with sparingly soluble compounds and requires high-throughput technology to rapidly and accurately determine the pKa values of drug candidates. In this chapter, on the one hand, the challenge of pKa determination in hydroorganic solvents and the most widely used approaches to obtain the aqueous extrapolated value are presented. On the other hand, high-throughput methods based on potentiometry, spectrophotometry, and capillary electrophoresis are discussed and compared.

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, 2015

This chapter reviews the most used classical methods, potentiometry and spectrophotometry, for ac... more This chapter reviews the most used classical methods, potentiometry and spectrophotometry, for acidity constant determination. For this purpose, the theoretical and operational definitions of pH and the equations to calculate acidity constants from potentiometric and spectrophotometric data are explained. In addition, capillary electrophoresis is presented as a very convenient technique for pKa determination, especially in the case of low-purity samples.