Identificador: TDX:783
Autores: Pasamontes Fúnez, Alberto
Resumen:
The objective of this thesis is to study and develop analytical methods to determineamoxicillin and clavulanic acid in pharmaceuticals using sequential injection analysis (SIA)with a diode-array spectrophotometric detector to obtain second-order data. To treat thesedata, the chemometric tool used was; multivariate curve resolution with alternating leastsquares (MCR-ALS) and the techniques involved in the resolution process are: principalanalysis components (PCA) and simple-to-use interactive self-modelling mixture analysis(SIMPLISMA).The first chapter contains a brief description of the theoretical backgrounds thathave been used during this thesis. We explain the characteristics and properties ofamoxicillin and clavulanic acid, we describes the instrumental and the chemometric toolsused and at the end, we introduce the experimental designs used and the desirabilityfunction.In the next two chapters contain the bulk of the work carried out for this thesis andincorporate papers published in journals. In the first paper, the pharmaceuticals wereclassified according to their selective zones in order to propose the type of calibration. In aprevious step, the experimental work was conducted to find an analytical sequence thatallows us to obtain an evolving system. This step was carried out using experimentaldesign. In the second paper, the quantity of amoxicillin in the pharmaceuticals withinterferents or without selective zones was determined. To carry out correctly thecalibration step, we studied different conditions related to the MCR-ALS process.In the third paper, we propose the simultaneous determination of amoxicillin andclavulanic acid which they have the acid-base characteristics and spectral profile similar.To determine both analytes, a new analytical sequence was redesigned. In the fourthpaper, we describe the state of the art of sequential injection analysis (SIA) andmultivariate curve resolution with alternating least squares (MCR-ALS) by reviewing thebibliography since 2004. We discuss the potential of SIA for generating second-orderdata.In previous papers, we found that the most critical step in the development ofanalytical methods based on SIA and MCR-ALS was to obtain an analytical sequence thatprovides an evolving system. To resolve so, we developed the method of experimentaldesign to obtain the optimal analytical sequence.In the forth paper, we studied all the factors and analysed how they affect to theanalytical sequence. We also proposed responses to quantitatively represent a goodresolution. Once these factors and responses were proposed, we used a Plackett-Burmandesign to remove the non-relevant factors and then modelled a response surface. In themaximum of response surface, the optimum conditions for the analytical sequence couldbe visualised. To transform several responses into a single response, we used the overalldesirability function. In the sixth paper, we applied an alternative optimisation methodknows as the simplex approach. We aimed to determine amoxicillin and clavulanic acidsimultaneously when the number of factors and responses was higher than in theprevious paper.The last chapter contains the conclusions of the thesis. In general, we concludethat a combined sequential injection analysis (SIA) with a multivariate detector (i.e. diodearray spectrophotometer) and multivariate curve resolution with alternating least squares(MCR-ALS) can be used for both qualitative and quantitative analyses since, it providesconcentration and spectra profiles for the different species of the sample.
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