State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

Polysaccharide-based chiral stationary phases have been recognized as one of the most powerful ones for high performance liquid chromatography (HPLC) separations of chiral compounds in analytical and also in preparative scale. Immobilized polysaccharide-based chiral stationary phases constitute a remarkable achievement due to their stable nature on working with standard or common solvents and also with those prohibited for using with coated phases. This review is mainly focused on the i. applications of these chiral stationary phases in numerous fields of HPLC separations; ii. comparative aspects between immobilized vs. coated polysaccharide-derived phases, and iii. revision of several theoretical studies such as enantiorecognition mechanism, mobile phase composition and column temperature effects.Laboratorio de Investigación y Desarrollo de Métodos Analíticos (LIDMA

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

Polysaccharide-based chiral stationary phases have been recognized as one of the most powerful ones for high performance liquid chromatography (HPLC) separations of chiral compounds in analytical and also in preparative scale. Immobilized polysaccharide-based chiral stationary phases constitute a remarkable achievement due to their stable nature on working with standard or common solvents and also with those prohibited for using with coated phases. This review is mainly focused on the i. applications of these chiral stationary phases in numerous fields of HPLC separations; ii. comparative aspects between immobilized vs. coated polysaccharide-derived phases, and iii. revision of several theoretical studies such as enantiorecognition mechanism, mobile phase composition and column temperature effects.Fil: Padró, Juan Manuel. 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; Argentin

Coeficientes de partición entre líquidos iónicos y agua : Aplicación a la microextracción dispersiva de compuestos antichagásicos en muestras biológicas

El objetivo de este trabajo de tesis es obtener coeficientes de partición para analitos de diversa naturaleza química entre líquidos iónicos a temperatura ambiente y soluciones acuosas. Emplear estos coeficientes en el “Modelo del Parámetro de Solvatación” con la finalidad de predecir extracciones desde matrices acuosas con altos factores de recuperación. Emplear los resultados obtenidos en la “microextracción líquido-líquido iónico dispersiva” de compuestos antichagásicos (benznidazol y nifurtimox) presentes en plasma humano y leche materna.Facultad de Ciencias Exacta

Development of an ionic liquid-based dispersive liquid–liquid microextraction method for the determination of nifurtimox and benznidazole in human plasma

Dispersive ionic liquid–liquid microextraction combined with liquid chromatography and UV detection was used for the determination of two antichagasic drugs in human plasma: nifurtimox and benznidazole. The effects of experimental parameters on extraction efficiency—the type and volume of ionic liquid and disperser solvent, pH, nature and concentration of salt, and the time for centrifugation and extraction—were investigated and optimized. Matrix effects were detected and thus the standard addition method was used for quantification. This microextraction procedure yielded significant improvements over those previously reported in the literature and has several advantages, including high inter-day reproducibility (relative standard deviation¼1.02% and 3.66% for nifurtimox and benznidazole, respectively), extremely low detection limits (15.7 ng mL1 and 26.5 ng mL1 for nifurtimox and benznidazole, respectively), and minimal amounts of sample and extraction solvent required. Recoveries were high (98.0% and 79.8% for nifurtimox and benznidazole, respectively). The proposed methodology offers the advantage of highly satisfactory performance in addition to being inexpensive, simple, and fast in the extraction and preconcentration of these antichagasic drugs from human-plasma samples, with these characteristics being consistent with the practicability requirements in current clinical research or within the context of therapeutic monitoring.Fil: Padró, Juan Manuel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Grupo Cromatografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marsón, María Elena. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Servicios a la Industria y al Sistema Científico; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reta, Mario Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Grupo Cromatografía; Argentin

Predicting the partitioning of biological compounds between room-temperature ionic liquids and water by means of the solvation-parameter model

The partition coefficients, PIL/w, for different probe molecules as well as for compounds of biological interest between the room-temperature ionic liquids (RTILs) 1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], 1-hexyl-3-methylimidazolium hexafluorophosphate, [HMIM][PF6], 1-octyl-3-methylimidazolium tetrafluoroborate, [OMIM][BF4] and water were accurately measured. [BMIM][PF 6] and [OMIM][BF4] were synthesized by adapting a procedure from the literature to a simpler, single-vessel and faster methodology, with a much lesser consumption of organic solvent. We employed the solvation-parameter model to elucidate the general chemical interactions involved in RTIL/water partitioning. With this purpose, we have selected different solute descriptor parameters that measure polarity, polarizability, hydrogen-bond-donor and hydrogen-bond-acceptor interactions, and cavity formation for a set of specifically selected probe molecules (the training set). The obtained multiparametric equations were used to predict the partition coefficients for compounds not present in the training set (the test set), most being of biological interest. Partial solubility of the ionic liquid in water (and water into the ionic liquid) was taken into account to explain the obtained results. This fact has not been deeply considered up to date. Solute descriptors were obtained from the literature, when available, or else calculated through commercial software. An excellent agreement between calculated and experimental log PIL/w values was obtained, which demonstrated that the resulting multiparametric equations are robust and allow predicting partitioning for any organic molecule in the biphasic systems studied.Fil: Padró, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Ponzinibbio, Agustín. 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. Laboratorio de Estudio de Compuestos Orgánicos; ArgentinaFil: Agudelo Mesa, Leidy Bibiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Reta, Mario Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentin

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

Development of an ionic-liquid-based dispersive liquid–liquid microextraction method for the determination of antichagasic drugs in human breast milk. Optimization by central composite design

Chagas disease constitutes a major public health problem in Latin America. Human breast milk is a biological sample of great importance for the analysis of therapeutic drugs, as unwanted exposure through breast milk could result in pharmacological effects in the nursing infant. Thus, the goal of breast milk drug analysis is to inquire to which extent a neonate may be exposed to a drug during lactation. In this work, we developed an analytical technique to quantify benznidazole and nifurtimox (the two antichagasic drugs currently available for the medical treatment) in human breast milk, with a simple sample pre-treatment followed by an ionic-liquid-based dispersive liquid–liquid microextraction combined with high-performance liquid chromatography and UV detection. For this technique, the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate has been used as the “extraction solvent”. A central composite design was used to find the optimum values for the significant variables affecting the extraction process: volume of ionic liquid, volume of dispersant solvent, ionic strength, and pH. At the optimum working conditions, the average recoveries were 77.5 and 89.7%, the limits of detection were 0.06 and 0.09 μg mL-1 and the inter-day reproducibilities were 6.25 and 5.77% for benznidazole and nifurtimox, respectively. The proposed methodology can be considered sensitive, simple, robust, accurate, and green.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Exacta

Desarrollo de un método potenciométrico de alta eficiencia de procesamiento de datos para determinar pKa en varias composiciones de solvente y temperaturas : Aplicación a buffers de uso en HPLC compatibles con espectrometría de masas

La retención y selectividad de analitos en cromatografía de líquidos usualmente se controla mediante la optimización del pH y de la composición de solvente. Sin embargo, estas variables no son independientes, sino que la composición del solvente modifica el pKa de las sustancias disueltas en él y, en consecuencia, el pH del medio. De la misma manera, la temperatura también puede variar el pKa de las sustancias afectando el pH de las fases móviles cromatográficas y los grados de disociación de los analitos.Facultad de Ciencias Exacta

Fluorine Labeling of Nanoparticles and In Vivo 19F Magnetic Resonance Imaging

Fluorinated nanoparticles have increasing applications, but they are still challenging to prepare, especially in the case of water-soluble fluorinated nanoparticles. Herein, a fluorine labeling strategy is presented that is based on the conjugation of custom-made small fluorinated building blocks, obtained by simple synthetic transformations, with carboxylated gold nanoparticles through a convenient phase-transfer process. The synthesis of four fluorinated building blocks with different chemical shifts in 19F nuclear magnetic resonance and varied functionalities is reported, along with their conjugation onto nanoparticles. Fluorinated nanoparticles of small core size obtained by this conjugation methodology and by direct synthesis presented high transverse relaxation times (T2) ranging from 518 to 1030 ms, and a large number of equivalent fluorine atoms per nanoparticle (340-1260 fluorine atoms), which made them potential candidates for 19F magnetic resonance related applications. Finally, nontargeted fluorinated nanoparticles were probed by performing in vivo 19F magnetic resonance spectroscopy (19F MRS) in mice. Nanoparticles were detected at both 1 and 2 h after being injected. 19F MRI images were also acquired after either intravenous or subcutaneous injection. Their fate was studied by analyzing the gold content in tissues by ICP-MS. Thus, the present work provides a general fluorination strategy for nanoparticles and shows the potential use of small fluorinated nanoparticles in magnetic-resonance-related applicationsThis work was supported in part by grants from the Spanish State Research Agency (MCI/PID2019-107449RB-I00/AEI/10.13039/501100011033, RYC-2017-22412, and SAF2017-84494-C2-R), from the Fundación Biofísica Bizkaia, the Basque Excellence Research Centre (BERC) program, and projects IT1196-19 and Grant KK-2019/bmG19 of the Basque Government. We also thank the UE for funding (Nova MRI, H2020-MSCA-ITN-2018-811382). This work was performed under the Maria de Maeztu Units of Excellence Programme Grant MDM-2017-0720 ministry of Science, Innovation and Universities. The authors thank for technical and human support the Materials and Surfaces Service and the Central Analysis Service of Bizkaia provided by SGIker (UPV/EHU) and European funding (ERDF and ESF) for the XPS, TEM and ICP-AES analyses. The MRI service members of CIC biomaGUNE are also acknowledged for their support of the in vivo experiment

Development of an ionic liquid-based dispersive liquid–liquid microextraction method for the determination of nifurtimox and benznidazole in human plasma

Dispersive ionic liquid–liquid microextraction combined with liquid chromatography and UV detection was used for the determination of two antichagasic drugs in human plasma: nifurtimox and benznidazole. The effects of experimental parameters on extraction efficiency—the type and volume of ionic liquid and disperser solvent, pH, nature and concentration of salt, and the time for centrifugation and extraction—were investigated and optimized. Matrix effects were detected and thus the standard addition method was used for quantification. This microextraction procedure yielded significant improvements over those previously reported in the literature and has several advantages, including high inter-day reproducibility (relative standard deviation=1.02% and 3.66% for nifurtimox and benznidazole, respectively), extremely low detection limits (15.7 ng mL −1 and 26.5 ng mL −1 for nifurtimox and benznidazole, respectively), and minimal amounts of sample and extraction solvent required. Recoveries were high (98.0% and 79.8% for nifurtimox and benznidazole, respectively). The proposed methodology offers the advantage of highly satisfactory performance in addition to being inexpensive, simple, and fast in the extraction and preconcentration of these antichagasic drugs from human-plasma samples, with these characteristics being consistent with the practicability requirements in current clinical research or within the context of therapeutic monitoring.Facultad de Ciencias Exacta