Determinación, mediante cromatografía de líquidos con detección fluorescente, de bisfenol A y fenol migrado desde juguetes y envases de suero

Recientemente ha resonado con fuerza en los medios de comunicación la posible peligrosidad para la salud humana, fundamentalmente en niños y bebés, derivada de la continua exposición al bisfenol A (BPA) migrado de objetos cotidianos fabricados con diversos tipos de plástico. Debido a su importancia, en el siguiente trabajo se ha determinado BPA y fenol migrado desde juguetes y envases de suero mediante cromatografía de líquidos de alta resolución acoplada a un detector de fluorescencia (HPLC-FLD). Mediante un diseño de experimentos D-óptimo, se han seleccionado las condiciones cromatográficas que permiten maximizar las áreas de pico y minimizar su tiempo de retención para garantizar una metodología lo más sensible y rápida posible. En estas condiciones, se han construido y validado los calibrados y se ha calculado el límite de decisión y la capacidad de detección en los límites establecidos para cada uno de los analitos estudiados y finalmente se ha determinado el contenido de fenol y BPA en las muestras problema

Kinetic models of migration of melamine and formaldehyde from melamine kitchenware with data of liquid chromatography

European legislation has established a specific migration limit (SML) of 15 mg kg−1 for formaldehyde and 2.5 mg kg−1 for melamine. Formaldehyde resins are used in the manufacture of melamine kitchenware. Formaldehyde is listed in group 1 of the IARC list of carcinogenic compounds. To determine the quantity of formaldehyde and melamine as potential migrants from different types of melamine kitchenware (glass, mug, cutlery, big cup and bowl), a HPLC-DAD method has been implemented. This method is an alternative to the ones proposed in technical guidelines to determine formaldehyde by UV–vis spectrophotometry and melamine by HPLC. The final objective was to fit the migration kinetic curves of these two analytes in melamine kitchenware. After the method was validated, decision limit (CCα) and detection capability (CCβ) were calculated for both analytes, when the probabilities of false positive (α) and false negative (β) were fixed at 0.05; being CCβ 0.269 mg L−1 and 0.311 mg L−1 for melamine and formaldehyde respectively. CCα and CCβ were also calculated at the SML of both analytes. The migration testing were conducted with simulant B (3% acetic acid (w/v) in aqueous solution), the conditions of each exposure being 70 °C for 2 h. The quantities of melamine and formaldehyde found in the third exposure of the total kitchenware analysed were between 0.21 and 1.09 mg L−1 and between 0.55 and 3.86 mg L−1, respectively. Migration kinetic curves were built for each type of kitchenware with the data of sixteen consecutive migration cycles (70 °C each 30 min). The SML for melamine was surpassed in the mug, in the big cup and in the bowl after eleven, thirteen and one cycles, respectively. When more cycles were carried out in the mug, the values of the accumulated quantity of formaldehyde and melamine were 15.30 and 6.79 mg L−1, respectively, after thirty-two cycles. Both concentrations exceeded the corresponding SML.MINECO (AEI/FEDER, UE) and Consejería de Educación de la Junta de Castilla y León through projects CTQ2017-88894-R and BU012P17 respectively (all co-financed with FEDER funds

Univariate data analysis versus multivariate approach in liquid chromatography. An application for melamine migration from food contact materials

The aim of this work is focused on the melamine migration from food contact materials (FCMs), considering data obtained from univariate analysis versus that obtained from multivariate approach in liquid chromatography coupled to diode array detector. Plastic food contact materials are made from monomers and additives. Moreover, non-intentionally added substances (NIAS) can be part of the composition of the FCM: raw material impurities or process by-products, inks or adhesives. Any compound present within a FCM can migrate to foodstuff. Specific migration of some substances from plastic FCMs to food/simulant is limited by European legislation in force (Commission Regulation No 10/2011). Quantification of analytes in migration samples through a univariate analysis could lead to erroneous results. As an example, in liquid chromatography NIAS can interfere when coeluting with analytes or when they have close retention time. In that case, an overestimation would happen and the verification of the compliance of the specific migration limit (SML) of a substance would be incorrect. A solution to the problem can be found in the application of a chemometric tool with the second-order advantage, which allows the unequivocal identification of analytes. Specifically, for this work, PARAFAC/ PARAFAC2 decomposition technique along with tensors arranged from HPLC-DAD data of migration (test and kinetics) samples were used for the identification and quantification of melamine. Results of melamine quantity found in migration samples from five types of melaware by means of a multivariate approach were compared to results obtained with a univariate data analysis carried out with values of chromatographic peak area as response. The comparison reveals that in test samples, univariate analysis supposes an overestimation in the quantity of melamine of 30 % on average, with respect of the concentration obtained from the multivariate approach. Besides, in kinetics samples it is remarkable that for one migration cycle the melamine found was 10 times above the one that obtained with PARAFAC decomposition. Summing up, multivariate data analysis of migration samples supposes a great advantage in order to comply with the established regulation about migrants and to decrease the false non-compliant results.The authors thank the Consejería de Educación de la Junta de Castilla y León, Spain for financial support through project BU052P20, cofinanced with FEDER funds. M.M. Arce wish to thank JCyL for her postdoctoral contract through project BU052P20

Procedure to explore a ternary mixture diagram to find the appropriate gradient profile in liquid chromatography with fluorescence detector. Application to determine four primary aromatic amines in napkins

The purpose of this work is to develop a tool to search for a gradient profile with ternary or binary mixtures in liquid chromatography, that can provide well-resolved chromatograms in the shortest time for multianalyte analysis. This approach is based exclusively on experimental data and does not require a retention time model of the compounds to be separated. The methodology has been applied for the quantification of four primary aromatic amines (PAAs) using HPLC with fluorescence detector (FLD). Aniline (ANL), 2,4-diaminotoluene (TDA), 4,4 -methylenedianiline (MDA) and 2-aminobiphenyl (ABP) have been selected since their importance in food contact materials (FCM). In order to achieve that, partial least squares (PLS) models have been fitted to relate CMP (control method parameters) and CQA (critical quality attributes). Specifically, PLS models have been fitted using 30 experiments for each one of the four CQA (resolution between peaks and total elution time), considering 33 predictor variables (the composition of the methanol and acetonitrile in the mobile phase and the time of each one of the 11 isocratic segments of the gradient). These models have been used to predict new candidate gradients, and then, some of those predictions (the ones with resolutions above 1.5, in absolute value, and final time lower than 20 min) have been experimentally validated. Detection capability of the method has been evaluated obtaining 1.8, 189.4, 28.8 and 3.0 μg L−1 for ANL, TDA, MDA and ABP, respectively. Finally, the application of chemometric tools like PARAFAC2 allowed the accurate quantification of ANL, TDA, MDA and ABP in paper napkins in the presence of other interfering substances coextracted in the sample preparation process. ANL has been detected in the three napkins analysed in quantities between 33.5 and 619.3 μg L−1, while TDA is present in only two napkins in quantities between 725.9 and 1908 μg L−1. In every case, the amount of PAAs found, exceeded the migration limits established in European regulations.The authors thank the Consejería de Educación de la Junta de Castilla y León for financial support through project BU052P20, cofinanced with FEDER funds. M.M. Arce wish to thank JCyL for her postdoctoral contract through project BU052P20

Method operable design region obtained with a partial least squares model inversion in the determination of ten polycyclic aromatic hydrocarbons by liquid chromatography with fluorescence detection

A chromatographic method with the Analytical Quality by Design (AQbD) methodology is developed for the simultaneous determination by HPLC-FLD of ten PAHs (naphthalene, phenanthrene, anthracene, flu- oranthene, pyrene, chrysene, benzo[a]anthracene, perylene, benzo[b]fluoranthene, and benzo[a]pyrene), widely spread in the environment. The construction of the Method Operable Design Region (MODR) is conducted, for the first time, via the inversion of a multiresponse Partial Least Squares (PLS2) model, which is needed to maintain the correlations among the Critical Method Parameters (CMP), among the Critical Quality Attributes (CQA), and the covariance between one another. The five CMP considered were the composition of the mobile phase (water, methanol, acetonitrile), flow rate, and column temperature. The eight CQA were linked to resolution between peaks recorded in the same emission wavelength (greater than 1.4) and the total time (less than 15 minutes). By systematic use of experimental design and parallel coordinates plots to explore the Pareto optimal front obtained with the PLS2 model inversion, the computed MODR is formed by convex combinations of eight specific settings of Critical Method Parameters that have a mobile phase with percentages of water between 37 and 38 %, of methanol from 13 and 22 %, and of acetonitrile between 41 and 49 %, together with a flow rate between 1.47 and 1.50 mL min −1 , and column temperature between 41.9 and 44.0 °C in their adequate combinations. All the chromatographic peaks are well resolved, with total time varying between 12.96 and 15.66 min inside the estimated MODR and the analytical method is accurate with CC βbetween 0.9 and 7.0 μg L −1 with probability of both false positive and false negative equal to 0.05.Research projects CTQ2017-88894-R and BU052P20, financed by the Spanish Ministerio de Ciencia, Inno- vación y Universidades (AEI/FEDER, UE) and Consejería de Edu- cación de la Junta de Castilla y León, both co-financed with Eu- ropean Development Funds. M.M. Arce wishes to thank Junta de Castilla y León for her postdoctoral contract through BU052P20 project

A new approach based on inversion of a partial least squares model searching for a preset analytical target profile. Application to the determination of five bisphenols by liquid chromatography with diode array detector

The paper shows a procedure for selecting the control method parameters (factors) to obtain a preset ‘analytical target profile’ when a liquid chromatographic technique is going to be carried out for the simultaneous determination of five bisphenols (bisphenol-A, bisphenol-S, bisphenol-F, bisphenol-Z and bisphenol-AF), some of them regulated by the European Union. The procedure has three steps. The first consists of building a D-optimal combined design (mixture-process design) for the control method parameters, which are the composition of the ternary mobile phase and its flow rate. The second step is to fit a PLS2 model to predict six analytical responses (namely, the resolution between each pair of consecutive peaks, and the initial and final chromatographic time) as a function of the control method parameters. The third final step is the inversion of the PLS2 model to obtain the conditions needed for attaining a preset analytical target profile. The computational inversion of the PLS2 prediction model looking for the Pareto front of these six responses provides a set of experimental conditions to conduct the chromatographic determination, specifically 22% of water, mixed with 58% methanol and 20% of acetonitrile, keeping the flow rate at 0.66 mL min−1. These conditions give a chromatogram with retention times of 2.180, 2.452, 2.764, 3.249 and 3.775 min for BPS, BPF, BPA, BPAF and BPZ, respectively, and excellent resolution among all the chromatographic peaks. Finally, the analytical method is validated under the selected experimental conditions, in terms of trueness and precision. In addition, the detection capability for the five bisphenols were: 596, 334, 424, 458 and 1156 μg L−1, with probabilities of false positive and of false negative equal to 0.05.Spanish MINECO (AEI/FEDER, UE) and Consejería de Educación de la JCyL through projects CTQ2017-88894-R and BU052P20, co-financed with European Regional Development Fund

Trabajos fin de grado/máster estructuralmente iguales y obligatoriamente diferentes ¿es posible?

Póster presentado en: VIII Jornadas de Innovación Docente de la UBU, Burgos, 5 de abril de 2016, organizadas por el Instituto de Formación e Innovación Educativa-IFIE de la Universidad de Burgo

Partial least squares model inversion in the chromatographic determination of triazines in water

Inside the framework of Analytical Quality by Design, a model-based approach has been developed and used to identify operating conditions (control method parameters) related to the composition and flow rate of the mobile phase for a liquid chromatographic determination with preset quality characteristics. The approach starts by defining these desired characteristics of the intended chromatogram (proper resolution for consecutive peaks and short time of analysis) and then looking for the needed control method parameters via inversion of a Partial Least Squares (PLS) prediction model. The procedure has been applied to the determination of eight triazines (simazine, simetryn, atrazine, ametryn, propazine, terbuthylazine, prometryn and terbutryn) in surface waters by means of SPE-HPLC-DAD. These triazines either are forbidden or have a maximum allowable limit due to their potential toxicity. The experimental verification of the selected parameters showed that the experimental results were significantly equal to those predicted. Besides, the validation of the developed method allowed concluding that accuracy was fulfilled for the eight triazines and there was not bias. With a probability of false positive equal to 0.05, CCβ was less than 3 µg L−1 for every triazine, except for simazine and terbutryn, which was less than 6 µg L−1 being the probability of false negative less than 10-6. No triazine was found, above their maximum allowable concentration, in any of the samples of surface water picked at fifteen different locations, mostly from streams and the Arlanzón river, near Burgos (Spain).Spanish MINECO (AEI/FEDER, UE) through project CTQ2017-88894-R, and Consejería de Educación de la Junta de Castilla y León (BU052P20) both co-financed with European Regional Development Fund

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Estrategias quimiométricas aplicadas a técnicas cromatográficas para el análisis de monómeros y aditivos

El eje central de la tesis de investigación consiste en la implementación de procedimientos analíticos, empleando como técnica de análisis la cromatografía líquida con distintos detectores (FLD y DAD), que presentan bajo impacto tanto medioambiental como económico. Los métodos desarrollados se han aplicado para la determinación de sustancias perjudiciales para la salud (mutágenos, carcinógenos o disruptores endocrinos) en materiales de uso cotidiano, focalizado en el ámbito del cumplimento de las regulaciones vigentes referentes a migrantes. Las muestras de migración habitualmente presentan matrices complejas, en gran parte motivada por los diferentes componentes (monómeros, aditivos, impurezas, NIAS, etc.) que forman parte de los materiales a partir de los cuales se obtienen las muestras. He aquí dónde toma especial relevancia la identificación inequívoca de los analitos de interés junto con el cumplimiento de los criterios de funcionamiento de los métodos analíticos siguiendo normativas europeas. Con este objetivo, se han utilizado distintas herramientas quimiométricas multivariantes (PARAFAC, PARAFAC2, diseños D-óptimos, frente Pareto, algoritmos genéticos, coordenadas paralelas) para obtener la información útil contenida en la ingente cantidad de datos que se obtiene en cada análisis cromatográfico