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Chiral separation of diquats and determination of stability constants of their complexes with cyclodextrins by capillary electrophoresis
Bílek, Jan ; Kašička, Václav (advisor) ; Jelínek, Ivan (referee)
Capillary zone electrophoresis was used for chiral separation of eleven diquat derivatives. These N-heteroaromatic dications containing structural motif of 2,2'-bipyridine have recently been studied for their interesting electrochemical properties as well as for the axial chirality of their molecules. The combination of these properties could potencially lead to interesting applications in the future. For enantioseparation of diquats (DQ) commercially available randomly sulfated α-, β-, and γ-cyclodextrins with high degree of substitution were used. A succesfull chiral separation was achieved using all of the three sulfated cyclodextrins as chiral selectors (CS). Baseline enantioseparation was achieved for 82 %, 91 % respectively 100 % of the analyzed DQ in the presence of HS-α-CD, HS-β-CD, HS-γ-CD respectively. The highest separation efficiency and resolution were obtained in the backround electrolyte containing 22 mmol/L NaOH, 35 mmol/L H3PO4 (pH2,5) and 6 mmol/L HS-β-CD. Using three available nonracemic DQ an identification of the particular M- and P-enantiomers was done for the three corresponding DQ structures. Apparent stabillity constants of complexes of the DQ derivatives with above mentioned cyclodextrins as CS were determined by means of capillary affinity electrophoresis. The stability...
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Application of Mass Spectrometry for Analysis of Biologically Active and Clinically Significant Compounds.
Štícha, Martin ; Jelínek, Ivan (advisor) ; Smrček, Stanislav (referee) ; Tůma, Petr (referee)
- 8 - ABSTRACT (EN) The thesis is submitted as a commented set of reviewed publications documenting and depicting the possibilities of mass spectrometry in the field of chemical, biological and pharmaceutical research; namely for the purposes of structure elucidation of selected organometallic complexes, analyses of drugs and their metabolites, monitoring of important biological markers. In course of experimental work, the following objectives were studied and solved: Proposal and realization of micro-scale preparation of selected rhenium complexes with aromatic ligands, utilizing tetrabutyammonium tetrachlorooxorhenate as a starting material; preparation and structure characterization of oxorhenium(V) complexes with 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3- dihydroxynaphtalene as ligands by means of ESI/MS, APPI/MS and LDI-MS; ESI/MS and UV/Vis study of kinetic behavior of complexes arising from the reaction of tetrabutylamonnium tetrachlooxorhenate with pyrogallol and catechol as ligands. Special aim was devoted to the study of subsequent chemical transformation of primarily formed Re(V) complexes; structure characterization of selected ferrocene complexes with copper, gold and silver by means of ESI/MS. Proposal of methodology of structure characterization and quantification of the...
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Chiral separation of acyclic nucleoside phosphonates and determination of association constants of their complexes with cyclodextrins by capillary electrophoresis
Mikysková, Hana ; Coufal, Pavel (advisor) ; Jelínek, Ivan (referee)
Capillary electrophoresis (CE) has been applied to the chiral separation of acyclic nucleoside phosphonates, which belong toof the most important already registered or potential antiviral drugs. For enantioseparation of acyclic nucleoside phosphonates, the following native and derivatized cyclodextrin were used as chiral selectors: cyclodextrin, cyclodextrin, cyclodextrin, heptakis(2,6dimethyl) cyclodextrin, 2hydroxypropylcyclodextrin and quaternary ammonium cyclodextrine). The best resolution of (R,S)enantiomers of acyclic nucleoside phosphonates was achieved in basic backgroung electrolyte composed of 35 mM sodium tetraborate; pH 10, with addition of 17.6 mM cyclodextrin or 10 mM quaternary ammonium cyclodextrin chiral selectors. Capillary electrophoresis has been employed for determination of association constants of complexes of acyclic nucleoside phosphonate enantiomers with above mentioned chiral selectors. The association constants were determined by nonlinear regression analysis from the experimentally measured dependence of effective electrophoretic mobilities of the analytes on concentration of the chiral selector in the background electrolyte. Prior to association constant calculation, the effective electrophoretic mobilities were corrected to reference temperature,...
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Study of release kinetics of hydrophobic drug paclitaxel into hydrogels.
Batěk, Jan ; Bosáková, Zuzana (advisor) ; Jelínek, Ivan (referee)
In this diploma thesis, hydrogels based on 2-hydroxymethacrylate (HEMA) were studied. Their possible use to study the release kinetics of the hydrophobic anticancer drug paclitaxel (PTX) was investigated in order to approach the conditions simulating in vivo environments. Paclitaxel is a drug with strong side effects, which can be partially prevented by appropriate local application. In this work, polylatide (PLA) nanofibers with incorporated drug was studied. Furthermore, the effect of the addition of polyethylene glycol (PEG) with a molecular weight of 20 kDa and CD to the structure of PLA nanofibers on the profiles of PTX release into various environments simulating in vivo environments was studied. An analytical HPLC method with UV detection was used to monitor the release kinetics of PTX. The addition of PEG to PLA nanofibers resulted in a significantly higher amount of hydrophobic drug released, which was also released over a longer period of time, compared to fibers containing only PTX. This trend was evident in both experiments monitoring the release of PTX into PBS and into hydrogel matrices. The effect of CD addition on PTX release was evident only in monitoring the kinetics of PTX release into hydrogel matrices, where there was a greater release of PTX from these fibers. An increase in...
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Fast methods for analysis of migrants from food-contact materials
Vavrouš, Adam ; Čabala, Radomír (advisor) ; Jelínek, Ivan (referee) ; Bajerová, Petra (referee)
(AJ) Food contact materials pose a risk to human health due to a variety of contaminants which they can release into food. These compounds, migrants, include aromatic hydrocarbons, dialkyl phthalates, bisphenols, printing ink photoinitiators, and perfluoroalkyl compounds. The determination of all these substances can be expensive and time-consuming since universally applicable analytical approaches are not available nowadays. This work attempted to develop methods for the simultaneous determination of migrants from all of the mentioned groups in paper-based food contact materials and fatty food. A total of 68 contaminants were studied in paper products using liquid chromatography and gas chromatography coupled with tandem mass spectrometry detection. All analytes were isolated simultaneously using the modified "QuEChERS" method. This method demonstrated acceptable recovery and repeatability for most analytes in the validation study; LOQs ranged from 1.3 to 220 µg/kg. Analysis of 132 real paper products confirmed the occurrence of almost all studied analytes, which were often present in complex mixtures and at concentrations up to 628 mg/kg. A total of 41 potential contaminants were monitored in fatty foods by liquid chromatography with tandem mass detection. Contamination of the mobile phase by...
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Study of sensory-active compounds of hops in dry-hopped beers
Zlochová, Tereza ; Sobotníková, Jana (advisor) ; Jelínek, Ivan (referee)
Study of sensory-active compounds of hops in dry-hopped beers Key words: hop, hop oils, dry-hopping, beer, beer-aging, beer sensory analysis Nowadays, dry-hopping is a widely used method of beer making, with its pros and cons. The main purpose of dry-hopping is to derive specific hop aroma to beer in its very unchanged form. The essential part of this work consists of a study of hop essential oils, as the main providers of desired hop aroma. Firstly, the validation of methods for isolating essential oils from hop material and beer is carried out. Secondly, the transfer of these volatiles in process of dry-hopping is studied and the impact on beer aroma profile is discussed. Subsequently, changes of essential oils profile during beer-aging are observed and evaluated with a valuable tool, the sensory analysis. This study was realized on beer samples from Brewers' Choice program, thanks to the Research Institute of Brewing and Malting and Lenka Strakova, the Pilsner Urquell brewer.
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Electrochemical generation of tellurium volatile compounds with atomic absorption spectrometry
Labancová, Katarína ; Hraníček, Jakub (advisor) ; Jelínek, Ivan (referee)
EN The present diploma thesis deals with the electrochemical generation of volatile tellurium compounds in connection with atomic absorption spectrometry with the main goal to increase the response of the tellurium signals and thus expand the existing knowledge about this element. Tellurium is one of the heavier elements that forms less stable volatile compounds. The reason for choosing these elements was the fact that its concentration increases mainly in landfills where it is released into the environment, which can have an ecological impact and an impact on human health. In the first step, two types of electrochemical cells were constructed - a thin-film flow electrochemical cell with and without an ion exchange membrane and an apparatus with a flow injection arrangement. The choice of cell types, cathode and anode material and apparatus design was chosen based on a literature research. Attention was paid to the optimization of reaction conditions for electrochemical generation of volatile tellurium compounds, which significantly affect the efficiency of generation using a heated quartz tube atomizer. The optimized parameters were electrolyte concentration, carrier gas volume flow rate, electrolyte volume flow rate and generation current. In the second step, the effect of the temperature of the...
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Characterization of new complex-forming agents for CZE
Málková, Nikola ; Jelínek, Ivan (advisor) ; Dian, Juraj (referee)
This diploma thesis is focused on the use of modern instrumental analytical techniques for analytical evaluation and study of new complex-forming agents. Precise characterization of complex-forming agents is necessary to determine their potential use in scientific researches. These compounds are often used in analytical chemistry e.g. for kinetic determination of metal ions, as reagents for complexometric titrations and also for chiral separations of enantiomers. The dependences of effective electrophoretic mobilities of newly synthesized macrocyclic complex-forming agents on pH of a background electrolyte were measured by using CZE. This dependency is discussed further in the thesis. The thermodynamic dissociation constants of the studied compounds were determined too. Analysis by molecular UV/VIS spectrometry, infrared spectroscopy and mass spectrometry were also performed. The addition of the studied complex-forming agents to the separation of a mixed sample of fumaric acid and maleic acid was also studied. Knowledge of the chemical and physical properties of new substances contributes to the understanding of their chemical behavior and the determination of their application. This knowledge can be also very useful in scientific research, which these compounds are already involved in....
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Utilization of LC-MS/MS in diagnosis of congenital adrenal hyperplasia
Grúlová, Kristýna ; Kozlík, Petr (advisor) ; Jelínek, Ivan (referee)
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease that causes a disorder of steroidogenesis in the adrenal cortex. This disease is a part of a panel of diseases searched in preclinical nationwide neonatal screening. The methodology is based on measuring the concentration of 17-hydroxyprogesterone (17-OHP) in a dried blood spot using fluorescence immunoassay (FIA). However, this determination is not entirely specific and generates a high rate of false positive results (up to 4.3 %). In this diploma thesis the LC-MS / MS method was developed. This method measures selected steroid hormones involved in cortisol metabolism with respect to the diagnosis of CAH disease. The method was validated and applied to clinical samples, it identified CAH patients from negative controls and significantly reduced the false positivity of neonatal screening results. Compared to the FIA results, the LC-MS / MS method reduced false positivity up to 50 % by evaluating the concentration of 17-OHP. Moreover, by extending the diagnostic algorithm with other measured markers, the reduction was enhanced up to 98%. The developed method is also applicable for the measurement of serum and plasma samples, respectively, and has become a part of the confirmation tests for suspected CAH screening findings. Key...
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Fast methods for analysis of migrants from food-contact materials
Vavrouš, Adam ; Čabala, Radomír (advisor) ; Jelínek, Ivan (referee) ; Bajerová, Petra (referee)
(AJ) Food contact materials pose a risk to human health due to a variety of contaminants which they can release into food. These compounds, migrants, include aromatic hydrocarbons, dialkyl phthalates, bisphenols, printing ink photoinitiators, and perfluoroalkyl compounds. The determination of all these substances can be expensive and time-consuming since universally applicable analytical approaches are not available nowadays. This work attempted to develop methods for the simultaneous determination of migrants from all of the mentioned groups in paper-based food contact materials and fatty food. A total of 68 contaminants were studied in paper products using liquid chromatography and gas chromatography coupled with tandem mass spectrometry detection. All analytes were isolated simultaneously using the modified "QuEChERS" method. This method demonstrated acceptable recovery and repeatability for most analytes in the validation study; LOQs ranged from 1.3 to 220 µg/kg. Analysis of 132 real paper products confirmed the occurrence of almost all studied analytes, which were often present in complex mixtures and at concentrations up to 628 mg/kg. A total of 41 potential contaminants were monitored in fatty foods by liquid chromatography with tandem mass detection. Contamination of the mobile phase by...
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