[The applications of chiroptical spectroscopy for the determination and the detection of steroids and for the examination of their cyclodextrin-mediated enantioselective solubility]. / A kiroptikai spektroszkópia alkalmazása szteroidok meghatározására es elválasztásuk detektálására, valamint ciklodextrinekkel történo enantioszelektív oldhatóságuk tanulmányozására.

Chiroptical spectroscopy is one of the most developing areas of chiral analysis which role has been enhanced in recent years. In the thesis new applications of circular dichroism (CD) and optical rotatory dispersion (ORD) methods are presented via some examples. A quick and accurate CD spectroscopic method was developed for the simultaneous determination of ethisterone and its delta5-isomer (delta5-ethisterone). The method is based on the selective negative Cotton effect of the delta4-3-oxo group of ethisterone. The concentrations of the two isomers can be easily determined by ellipticity measurements at two different wavelengths without the application of any separation technique. CD detection for the separation of ethisterone isomers by high performance liquid chromatography (HPLC) is suitable even for the determination of the delta5-ethisterone, that contains isolated oxo groups. The separation of dehydroepiandrosterone (DHEA), dehydroepi-androsterone sulfate (DHEA-S) and related steroids was also elaborated by a CD detected HPLC technique. CD detection is a good tool for the determination of saturated ketones. Enantioselectivity was observed when the solubility of raceme norgestrel was examined in aqueous solutions of gamma-cyclodextrin and hydroxypropyl-gamma-cyclodextrin. A CD spectroscopic method, based on the measurement of g-factor was applied for the determination of the enantiomer ratio obtained. Levonorgestrel, the effective enantiomer was dissolved in greater extent using either cyclodextrins. The obtained solubility of norgestrel was greater using gamma-cyclodextrin, although the enantioselectivity was more significant when hydroxypropyl-gamma-cyclodextrin was applied. Phase-solubility examinations were appropriate for the verification of 1:1 stoichiometry and that the enantiomer ratios were independent of the cyclodextrin concentrations. A new calculation method was also elaborated, suitable for the direct determination of the concentrations of norgestrel enantiomers in aqueous cyclodextrin solutions.

Tracking of enantioselective solubility of rac-norgestrel in the presence of cyclodextrin by a CD spectroscopic method.

Dissolution of hydrophobic rac-norgestrel in aqueous gamma-cyclodextrin (gamma-CyD) and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CyD) solutions was investigated, and enantioselective dissolution was observed. (-)-Norgestrel, the eutomer molecule, was dissolved to a greater extent using each of the CyDs, although the effect was more significant in the case of HP-gamma-CyD. A circular dichroism (CD) spectroscopic method based on measurement of the anisotropy factor was applied for the determination of the enantiomer ratio. The concentration and the enantiomer ratio of norgestrel were determined indirectly in octanol after extraction. Optical rotation dispersion (ORD) measurements could confirm that neither the free CyDs nor their inclusion complexes could get into the organic phase during transport to octanol. Only the norgestrel molecules were able to get into the organic phase, although the enantiomer ratio remained the same as was obtained in the aqueous CyD solution.