Ανάπτυξη νέων αναλυτικών μεθόδων με την τεχνική της HPLC-ELSD γιά τον προσδιορισμό φαρμακευτικών ουσιών

Abstract

The subject of the Thesis is to investigate the use of the quasi-universal Evaporative Light Scattering Detector (ELSD) in the determination of some common metals found in pharmaceuticals, biological and environmental samples. In an attempt to study the effect of relative atomic mass (Ar) on the detector’s response A (equation A=α·mb), in relation to the composition of the mobile phase, the cations of IA and IIA groups of the Periodic Table are chosen. The study uses a FIA–ELSD setup without separation column and four different carrier solvents. The obtained observations are used for the determination of the metals in the following chapters.Lithium is the first of the cations to be studied. There have been developed and validated two LC-ELSD methods for the determination of lithium salts in two pharmaceutical formulations, blood plasma and urine. The first method uses a C18 separation column with an ion-pair reversed phase mechanism, while the second one uses a cation-exchange column CS14. Both methods show good linearity and sensitivity.Aluminum, in the form of Al(OH)3, is determined by using an ion-pair mechanism. The method is applied in three formulations, two chewable tablets and an oral suspension. There have been developed two methods, by applying several dissolution protocols, due to the differences in the pharmaceuticals’ composition. The results show remarkable fluctuations, due to the heterogeneity of the sample and the sampling procedure.In the following chapter, there have been developed two methods, one by using a cation-exchange and the other by using a C18 separation column, for the determination of zinc ions in an injectable insulin suspension. The amount of total and free zinc, are determined, and the results comply with European Pharmacopoeia specifications. Comparison of the proposed method with the reference method, AAS, shows that although the HPLC-ELSD method lacks sensitivity, can give reliable results for the injectable insulin formulation.In the last chapter there have been developed methods for the determination of ions in drinking water. Na+, K+, Mg2+ and Ca2+ ions are determined with the use of a cation-exchange column. The method is applied in HPLC laboratory-water, in commercial brands of mineral water, in samples from the main water supply and in an injectable formulation of saline physiological serum. There has also been developed a method for the determination of Cr(III) - Cr(VI), two pollutants found in drinking water, with the use of a cation-exchange column and a gradient elution program. Method is applied in water samples from the water supply of two different urban centers. Comparison of the HPLC-ELSD method with the official AAS method shows that the proposed one is much less sensitive but determines simultaneously Cr(VI) and Cr(III) in one single run without tedious pretreatment of the samples. Thus could be satisfactorily used in heavily polluted water or in samples after preconcentration.