Scope of partial least-squares regression applied to the enantiomeric composition determination of ketoprofen from strongly overlapped chromatographic profiles

Valuable quantitative information could be obtained from strongly overlapped chromatographic profiles of two enantiomers by using proper chemometric methods. Complete separation profiles where the peaks are fully resolved are difficult to achieve in chiral separation methods, and this becomes a particularly severe problem in case that the analyst need to measure the chiral purity, i.e., when one of the enantiomers is present in the sample in very low concentrations. In this report, we explore the scope of a multivariate chemometric technique based on unfolded partial least-squares regression, as a mathematical tool to solve this quite frequent difficulty. This technique was applied to obtain quantitative results from partially overlapped chromatographic profiles of R- and S-ketoprofen, with different values of enantioresolution factors (from 0.81 down to less than 0.2 resolution units), and also at several different S:R enantiomeric ratios. Enantiomeric purity below 1% was determined with excellent precision even from almost completely overlapped signals. All these assays were tested on the most demanding condition, i.e., when the minor peak elutes immediately after the main peak. The results were validated using univariate calibration of completely resolved profiles and the method applied to the determination of enantiomeric purity of commercial pharmaceuticals.Laboratorio de Investigación y Desarrollo de Métodos Analíticos (LIDMA

Bioactividad y análisis fitoquímico preliminar de la especie cordia spinescens boraginaceae, empleada como medicinal en la región de Cordoba Quindío

El empleo de las plantas medicinales con fines curativos es una práctica que se ha utilizado desde tiempo inmemorial. Durante mucho tiempo los remedios naturales, basados en las plantas medicinales, fueron el principal e incluso el único recurso del que disponían los chamanes, brujos, curanderos, magos y en épocas más recientes los médicos. Esto hizo que se profundizara en el conocimiento de las especies vegetales que poseen propiedades medicinales y ampliar su experiencia en el empleo de los productos que de ellas se extraen. Colombia como uno de los países con mayor biodiversidad posee una flora rica en plantas utilizadas como medicinales que pueden tener gran valor terapéutico, la región del Quindío al poseer variedad de climas presenta un gran número de plantas utilizadas por los campesinos, basados en la sabiduría popular, como medicinales. Resulta de gran importancia investigar los componentes y bioactividad de dicha riqueza botánica. En este caso se trata de la especie Cordia spinescens, a la cual se le realiza una marcha fitoquímica preliminar, para determinar las posibles causas de su acción terapéutica y un examen de bioactividad en Artemia salina para hallar la dosis letal media, resultado que da un indicio sobre la actividad de los metabolitos secundarios de la planta en un ser vivo. El siguiente estudio tiene estos dos elementos como objetivos principales limitándose los métodos empleados a la caracterización de estructuras sin llegar a su elucidación.Introducción 01. Fototerapia 62. Fitoquímica 8PregradoQuímic

Chiral analysis of derivatized amino acids from kefir by gas chromatography

The amino acids present in the kefir samples were derivatized using different alkyl chloroformates combined with alcohols and chromatographed on a (3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E) chiral gas-liquid chromatographic column. The combination of derivatization reagents that led to better chromato- graphic performance for standard amino acid solutions was critically compared. All the chloroformate/alchohol mixtures lead to fast and quantitative reactions. However, the ethyl chloroformate/ethanolmixturewas selected since the number of enantioseparated amino acid derivativeswas higher. The derivatizationwas applied to samples of kefir grains grown in raw and in skimmed UHT milk. The samples were previously pretreated by elution froma low-pressure ion-exchange columns. Standard addition calibration curves have been used for the quantitative determinations of amino acid derivatives in both samples, and the figs. of merit of the proposed method have been assessed. The L-and D-configuration of D-and L-alanine, D-and L-valine,D-proline, L-threonine, aspartic and glutamic acids, methionine, and cysteine were detected and quantitatively determined.Fil: Menestrina, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Osorio Grisales, Jaiver. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Castells, Cecilia Beatriz Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentin

Effect of co-solvents in the enantioselective esterification of (R/S)-ibuprofen with ethanol

The commercial biocatalyst Novozym 435 was used for the kinetic resolution of (R/S)-ibuprofen by esterification with short chain alcohols (ethanol, 1-propanol and 2-propanol) in the absence of organic co-solvent. The best performance enzymatic was obtained by employing ethanol as reagent and solvent. Due to deleterious effect of this alcohol on the integrity of commercial biocatalyst previously reported are used different organic co-solvents (isooctane, n-hexane, carbon tetrachloride, ethyl acetate, acetonitrile and tetrahydrofuran) that allowed to reduce the volume of ethanol to be used. Thus, was evaluated the effect of the chemical nature of the co-solvent on enantioselective esterification of (R/S)-ibuprofen with ethanol. The results show that the best performance was obtained with the reaction system without co-solvent added, importantly for their sustainability and eco-compatibility. Also demonstrated the need to take into account multiple physic-chemical properties of the solvents to analyze their effects on biocatalysis.Fil: José, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; ArgentinaFil: Toledo, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; ArgentinaFil: Osorio Grisales, Jaiver. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Quimica; ArgentinaFil: Briand, Laura Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; Argentin

Measurements of association constants between enantiomers and chiral selectors by capillary gas chromatography. Theoretical and practical considerations

The association constants of several volatile enantiomers with octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin at temperatures between 50 and 100 °C were measured by gas–liquid chromatography using capillary columns coated with different amounts of chiral selector dissolved in polysiloxane OV-1701 and prepared with a precisely determined phase ratio. Simple expressions were deduced to estimate the apparent distribution constants from accurate hold-up and retention times along with that known phase ratio at each temperature. The enantiomer-chiral selector association constants were then calculated from the linear regression of the apparent constants as a function of the chiral selector concentration. One aim of this study consisted in discussing all the experimental uncertainties inherent in the determination of enantiomer/selector association constants with chiral analytes, and how these fundamental measurements can be performed precisely without resorting to the use of reference solutes.Fil: Lebed, Pablo Jorge. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Investigación y Desarrollo de Métodos Analíticos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Keunchkarian, Sonia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Investigación y Desarrollo de Métodos Analíticos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Osorio Grisales, Jaiver. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Investigación y Desarrollo de Métodos Analíticos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castells, Cecilia Beatriz Marta. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Laboratorio de Investigación y Desarrollo de Métodos Analíticos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Determination of enantiomeric composition of ibuprofen in pharmaceutical formulations by partial least-squares regression of strongly overlapped chromatographic profiles

In this report, we demonstrate how chiral liquid chromatography combined with multivariate chemometric techniques, specifically unfolded-partial least-squares regression (U-PLS), provides a powerful analytical methodology. Using U-PLS, strongly overlapped enantiomer profiles in a sample could be successfully processed and enantiomeric purity could be accurately determined without requiring baseline enantioresolution between peaks. The samples were partially enantioseparated with a permethyl-β-cyclodextrin chiral column under reversed-phase conditions. Signals detected with a diode-array detector within a wavelength range from 198 to 241nm were recorded, and the data were processed by a second-order multivariate algorithm to decrease detection limits. The R-(-)-enantiomer of ibuprofen in tablet formulation samples could be determined at the level of 0.5mgL-1 in the presence of 99.9% of the S-(+)-enantiomorph with relative prediction error within ±3%.Fil: Osorio Grisales, Jaiver. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Grupo Cromatografía; ArgentinaFil: Arancibia, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Castells, Cecilia Beatriz Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Grupo Cromatografía; ArgentinaFil: Olivieri, Alejandro Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin

Permethylated β-cyclodextrin in liquid poly(oxyethylene) as a stationary phase for capillary gas chromatography

This paper reports the study of poly(oxyethylene) as a solvent for heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (PM-β-CD) and the potential of these mixtures for constructing enantioselective gas chromatography columns. Enantioseparations of volatile racemic mixtures using capillaries coated with 10–50% PM-β-CD diluted in Carbowax 20M were evaluated. The influence of the polymer type on retention, separation and reproducibility over a period of time is critically discussed. The poly(oxyethylene)-based columns were also compared to columns prepared by dilution of PM-β-CD in two polysiloxanes, SE-30 and SE-54, at several temperatures. Finally, we evaluated a new stationary phase prepared by crosslinking the chiral selector to the poly(oxyethylene) matrix.Fil: Osorio Grisales, Jaiver. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Tecnología de Pinturas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones en Tecnología de Pinturas; ArgentinaFil: Lebed, Pablo Jorge. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Tecnología de Pinturas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones en Tecnología de Pinturas; ArgentinaFil: Keunchkarian, Sonia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Tecnología de Pinturas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones en Tecnología de Pinturas; ArgentinaFil: González, Francisco R.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Tecnología de Pinturas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones en Tecnología de Pinturas; ArgentinaFil: Castells, Cecilia Beatriz Marta. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Tecnología de Pinturas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones en Tecnología de Pinturas; Argentin

Enantiomeric analysis of overlapped chromatographic profiles in the presence of interferences. Determination of ibuprofen in a pharmaceutical formulation containing homatropine

In this work, we studied the combination of chemometric methods with chromatographic separations as a strategy applied to the analysis of enantiomers when complete enantioseparation is difficult or requires long analysis times and, in addition, the target signals have interference from the matrix. We present the determination of ibuprofen enantiomers in pharmaceutical formulations containing homatropine as interference by chiral HPLC-DAD detection in combination with partial least-squares algorithms. The method has been applied to samples containing enantiomeric ratios from 95:5 to 99.5:0.5 and coelution of interferents. The results were validated using univariate calibration and without homatropine. Relative error of the method was less than 4.0%, for both enantiomers. Limits of detection (LOD) and quantification (LOQ) for (S)-(+)-ibuprofen were 4.96 × 10−10 and 1.50 × 10−9 mol, respectively. LOD and LOQ for the R-(−)-ibuprofen were LOD = 1.60 × 10−11 mol and LOQ = 4.85 × 10−11 mol, respectively. Finally, the chemometric method was applied to the determination of enantiomeric purity of commercial pharmaceuticals. The ultimate goal of this research was the development of rapid, reliable, and robust methods for assessing enantiomeric purity by conventional diode array detector assisted by chemometric tools.Fil: Padró, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Osorio Grisales, Jaiver. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Arancibia, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Olivieri, Alejandro Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Castells, Cecilia Beatriz Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata; Argentin