Multivariate curve resolution applied sequential injection data. Analysis of amoxicillin and clavulanic acid
- Autores: Alberto Pasamontse Funez
- Directores de la Tesis: María Pilar Callao Lasmarías (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2006
- Idioma: español
- Tribunal Calificador de la Tesis: Marcel Blanco Romia (presid.), María Soledad Larrechi García (secret.), Francesc Xavier Rius Ferrus (voc.), Antonia Garrido Frenich (voc.), Arsenio Muñoz de la Peña Castrillo (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
- español
El objetivo de esta tesis ha sido estudiar y desarrollar metodologías analíticas usando un sistema de inyección secuencial (SIA) con un espectrofotómetro de diodos en fila para obtener datos de segundo orden, Para tratar estos datos, las herramientas quimiométricas usadas han sido; resolución de curvas multivariante mediante mínimos cuadrados alternados (MCR-ALS) y otras técnicas relacionadas a ésta como el análisis de componentes principales (PCA) y SIMPLISMA.
Esta metodología se aplicó a la determinación de amoxicilina y ácido clavulánico en medicamentos. El análisis de fármacos presenta interés en el control de calidad del propio producto y, si el método puesto a punto es relevante, conecta con otro ámbito de máximo interés como es el análisis clínico, para el estudio del efecto y/o evolución de fármacos en el cuerpo humano. Dentro de este campo de aplicación, el análisis de antibióticos es relevante por la gran aplicación de estos productos. Este objetivo viene justificado por el interés en disponer de métodos analíticos rápidos y automatizados, ya que lleva asociado una minimización de costes, disminución del tiempo de análisis y del gasto en reactivos, y seguridad a la hora de trabajar con sustancias tóxicas.
De una forma general se puede concluir que la combinación de un sistema de inyección secuencial (SIA) y una herramienta quimiométrica como la resolución de curvas multivariante mediante mínimos cuadrados alternados (MCR-ALS) puede ser usado tanto para realizar un análisis cualitativo y cuantitativo ya que proporciona información de los perfiles de concentración y perfiles espectrales de las diferentes especies a estudio.
- English
The objective of this thesis is to study and develop analytical methods to determine amoxicillin and clavulanic acid in pharmaceuticals using sequential injection analysis (SIA) with a diode-array spectrophotometric detector to obtain second-order data. To treat these data, the chemometric tool used was; multivariate curve resolution with alternating least squares (MCR-ALS) and the techniques involved in the resolution process are: principal analysis components (PCA) and simple-to-use interactive self-modelling mixture analysis (SIMPLISMA). The first chapter contains a brief description of the theoretical backgrounds that have been used during this thesis. We explain the characteristics and properties of amoxicillin and clavulanic acid, we describes the instrumental and the chemometric tools used and at the end, we introduce the experimental designs used and the desirability function. In the next two chapters contain the bulk of the work carried out for this thesis and incorporate papers published in journals. In the first paper, the pharmaceuticals were classified according to their selective zones in order to propose the type of calibration. In a previous step, the experimental work was conducted to find an analytical sequence that allows us to obtain an evolving system. This step was carried out using experimental design. In the second paper, the quantity of amoxicillin in the pharmaceuticals with interferents or without selective zones was determined. To carry out correctly the calibration step, we studied different conditions related to the MCR-ALS process. In the third paper, we propose the simultaneous determination of amoxicillin and clavulanic acid which they have the acid-base characteristics and spectral profile similar. To determine both analytes, a new analytical sequence was redesigned. In the fourth paper, we describe the state of the art of sequential injection analysis (SIA) and multivariate curve resolution with alternating least squares (MCR-ALS) by reviewing the bibliography since 2004. We discuss the potential of SIA for generating second-order data. In previous papers, we found that the most critical step in the development of analytical methods based on SIA and MCR-ALS was to obtain an analytical sequence that provides an evolving system. To resolve so, we developed the method of experimental design to obtain the optimal analytical sequence. In the forth paper, we studied all the factors and analysed how they affect to the analytical sequence. We also proposed responses to quantitatively represent a good resolution. Once these factors and responses were proposed, we used a Plackett-Burman design to remove the non-relevant factors and then modelled a response surface. In the maximum of response surface, the optimum conditions for the analytical sequence could be visualised. To transform several responses into a single response, we used the overall desirability function. In the sixth paper, we applied an alternative optimisation method knows as the simplex approach. We aimed to determine amoxicillin and clavulanic acid simultaneously when the number of factors and responses was higher than in the previous paper. The last chapter contains the conclusions of the thesis. In general, we conclude that a combined sequential injection analysis (SIA) with a multivariate detector (i.e. diode array spectrophotometer) and multivariate curve resolution with alternating least squares (MCR-ALS) can be used for both qualitative and quantitative analyses since, it provides concentration and spectra profiles for the different species of the sample.
- español
