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Search for an efficient cobalt chelator
Nosková, Karolína ; Mladěnka, Přemysl (advisor) ; Smutný, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Nosková Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Monika Moravcová, MSc. Title of diploma thesis: Search for an efficient cobalt chelator Cobalt, as part of vitamin B12, is an essential trace element for human organism. However, long-term exposure to high doses leads to toxicity. Chronic cobalt intoxication is currently most commonly observed after the implantation of cobalt-containing prostheses, which in some cases do not work properly and cobalt is released from them by mechanical friction or corrosion. That not only leads to a local reaction, but cobalt ions also enter the blood and lymphatic circulation and thus cause a systemic reaction. The intoxication is then manifested by neurological, cardiovascular and endocrine symptoms, which can lead to irreversible changes or even to the death. However, a chelator that would be able to effectively and selectively bind cobalt and thus effectively treat intoxication is not available in clinical practice. The aim of this thesis was a search for an efficient cobalt chelator among known metal chelators. Chelation was measured in vitro by a method based on spectrophotometric detection of unchelated cobalt ions at...
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Search for an efficient cobalt chelator
Nosková, Karolína ; Mladěnka, Přemysl (advisor) ; Smutný, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Nosková Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Monika Moravcová, MSc. Title of diploma thesis: Search for an efficient cobalt chelator Cobalt, as part of vitamin B12, is an essential trace element for human organism. However, long-term exposure to high doses leads to toxicity. Chronic cobalt intoxication is currently most commonly observed after the implantation of cobalt-containing prostheses, which in some cases do not work properly and cobalt is released from them by mechanical friction or corrosion. That not only leads to a local reaction, but cobalt ions also enter the blood and lymphatic circulation and thus cause a systemic reaction. The intoxication is then manifested by neurological, cardiovascular and endocrine symptoms, which can lead to irreversible changes or even to the death. However, a chelator that would be able to effectively and selectively bind cobalt and thus effectively treat intoxication is not available in clinical practice. The aim of this thesis was a search for an efficient cobalt chelator among known metal chelators. Chelation was measured in vitro by a method based on spectrophotometric detection of unchelated cobalt ions at...
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Utilization of statistical approach in development of HPLC methods
Vymyslický, Filip ; Křížek, Tomáš (advisor) ; Kozlík, Petr (referee)
The aim of this diploma thesis was to develop a systematic procedure for the development of HPLC methods using the design of experiments. The system was developed based on the development of three HPLC methods for the determination of the purity of active substances using the design of experiments approach. The HPLC method for determining the purity of esomeprazole was selected to develop the systematic process for the development of HPLC methods by statistical approach. Experimental space was explored to find more suitable separation conditions. The second method used to develop the systematic procedure was the method for determining the purity of bisoprolol. This method was converted to a column of smaller size and the composition of the aqueous part of mobile phase was modified compared with the original pharmacopoeial method. Experimental space was explored to find more suitable separation conditions using the design of experiments. Last the method for determining the purity of risperidone was chosen. The composition of the aqueous part of mobile phase was changed in contrast to the original pharmacopoeial method. Experimental space was explored to find more suitable separation conditions using the design of experiments. For all studied HPLC methods, the values of the monitored chromatographic...
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Development of instrumentation and high-throughput screening methods for peptide ligand discovery and validation
Kryštůfek, Robin ; Konvalinka, Jan (advisor) ; Jiráček, Jiří (referee)
Peptides are used as synthetically available and easily derivatizable scaffold upon which it is possible to develop ligands targeting broad spectrum of biological targets. A time-tested approach to peptide binder identification is the preparation and screening of combinatorial libraries. Bypassing of this complicated procedure is possible by using biological systems for presentation, identification and selection of peptides based on the principle of in vitro evolution - i.e. display techniques. There are two complementary automated solutions for peptide binder identification described in this work. First is the SPENSER parallel peptide synthesizer, developed as a part of this diploma project, which can be used for peptide ligand discovery and optimization as well as validation of ligands identified using display techniques. Several libraries consisting of a total of 1 052 peptides have been prepared and then used to describe its potential applications. A sample of 154 preparations, representing 14.6 % analytical coverage of the prepared libraries, showed an average purity of 67 ± 19 % according to LC-MS. The libraries presented illustrate that SPENSER is a suitable tool for the parallel synthesis of linear and disulfide-cyclized peptides with limited variability, or libraries consisting of short...
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HPLC analysis of drugs
Dohnalová, Monika ; Kubíček, Vladimír (advisor) ; Lázníčková, Alice (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Monika Dohnalová Supervisor: Ing. Vladimír Kubíček, CSc. Title of Diploma Thesis: HPLC analysis of drugs The diploma thesis deals with the development and optimization of HPLC method for simultaneous determination of selected polyphenolic compounds: apigenin, acteoside and luteolin. During the experiments, the most suitable conditions for separation were sought, various mobile phases and various types of gradient elution were tested. The Zorbax Eclipse XBD C18 column 250 x 4.6 mm; 5 µm was used for analysis. The detection was performed with diode array detector at wavelengths 249 nm and 350 nm,the column was thermostated at 30 řC. The injected volume was 10 µl. The best results were achieved using mobile phase consisting of acetonitrile and aqueous solution of formic acid (0.03 mol/l) at a flow rate 1ml/min.
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Utilization of statistical approach in development of HPLC methods
Vymyslický, Filip ; Křížek, Tomáš (advisor) ; Kozlík, Petr (referee)
The aim of this diploma thesis was to develop a systematic procedure for the development of HPLC methods using the design of experiments. The system was developed based on the development of three HPLC methods for the determination of the purity of active substances using the design of experiments approach. The HPLC method for determining the purity of esomeprazole was selected to develop the systematic process for the development of HPLC methods by statistical approach. Experimental space was explored to find more suitable separation conditions. The second method used to develop the systematic procedure was the method for determining the purity of bisoprolol. This method was converted to a column of smaller size and the composition of the aqueous part of mobile phase was modified compared with the original pharmacopoeial method. Experimental space was explored to find more suitable separation conditions using the design of experiments. Last the method for determining the purity of risperidone was chosen. The composition of the aqueous part of mobile phase was changed in contrast to the original pharmacopoeial method. Experimental space was explored to find more suitable separation conditions using the design of experiments. For all studied HPLC methods, the values of the monitored chromatographic...
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