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Optimization of separation conditions for HPCCC of paclitaxel
Havrlantová, Šárka ; Kučera, Radim (advisor) ; Šatínský, Dalibor (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Šárka Havrlantová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Name of diploma thesis: Optimization of separation conditions for HPCCC of paclitaxel The aim of this work is a feasibility study of natural substances isolation (in my case it is paclitaxel and its intermediate 10-deacetylbaccatin) using modern technique called High performance countercurrent chromatography (HPCCC) available in Teva in Opava. For this basic research it was necessary to study the literature and test various solvent systems. Chosen solvent systems were then tested together with natural substance in HPCCC, results were processed and discussed. Countercurrent chromatography is considered a modern separation technique based on two immiscible liquids. One of them is called a stationary phase and is held inside the column by centrifugal force, the second liquid is called a mobile phase and is pumped through the column. Then the injected liquid sample is also pumped through the column and depending on distribution coefficients the sample components are either held in the stationary phase or pass through the column and detector into fraction collector. Advantages of this method are e.g. total...
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Bioanalytical Evaluation of New Acetylcholinesterase Inhibitors
Mžik, Martin ; Palička, Vladimír (advisor) ; Kučera, Radim (referee)
6 SUMMARY Bioanalytical evaluation plays a pivotal role in preclinical research of new drugs, particularly in investigation of their pharmacokinetics and metabolism. Use of modern analytical approaches is indispensable; chromatography and mass spectrometry are the techniques of choice in this area of research. To obtain reliable data, the analytical methods must be validated. Several authorities - such as European Medicines Agency or Food and Drug Administration - have published recommendations on bioanalytical method validation. In its theoretical part, this dissertation deals with description of Alzheimer's dementia with special focus on treatment strategies. Further attention is paid to topics that are directly related to the experimental work - liquid chromatography, mass spectrometry, sample preparation, method validation and pharmacokinetics. The experimental part - a commentary on the author's published articles - consists of three units: I. bioanalytical evaluation of PC-37 and PC-48 - novel 7-methoxytacrine and donepezil-derived dual cholinesterase inhibitors, II. study of the transport of donepezil across the blood-brain barrier with focus on its structure and substructures and III. bioanalytical evaluation of S-K1025 and S-K1026 - new 7-methoxytacrine and tryptophan-derived dual cholinesterase...
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LC-HRMS analysis of selected antihypertensive drugs in biological material for compliance assessment
Tláskalová, Anna ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
5 ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Anna Tláskalová Supervisor - specialist: Mgr. Martin Mžik Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title: LC-HRMS analysis of selected antihypertensive drugs in biological material for compliance assessment About 40 % of Czech population between the ages of 25 and 64 suffer from arterial hypertension. Although an array of effective antihypertensives is available nowadays, optimal blood pressure during treatment is reached by mere 30 % of the patients. This is mainly due to the patients' poor adherence to the treatment, who use their medicaments incorrectly or not at all. The adherence of a patient to the treatment, as well as pharmacokinetics, represent the most significant source of variability of the answer to the treatment and notably influences its outcome. The monitoring of plasmatic levels of antihypertensives is one of the methods of modern medicine which enables both an effective supervision of the incorrectly compensated patients, and the adjustment of dosage scheme. This diploma thesis focuses on development and optimisation of extraction procedures for selected antihypertensives (amiloride, amlodipine, betaxolol, bisoprolol, carvedilol, celiprolol,...
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Bioanalytical Evaluation of New Acetylcholinesterase Inhibitors
Mžik, Martin ; Palička, Vladimír (advisor) ; Maier, Vítězslav (referee) ; Kučera, Radim (referee)
6 SUMMARY Bioanalytical evaluation plays a pivotal role in preclinical research of new drugs, particularly in investigation of their pharmacokinetics and metabolism. Use of modern analytical approaches is indispensable; chromatography and mass spectrometry are the techniques of choice in this area of research. To obtain reliable data, the analytical methods must be validated. Several authorities - such as European Medicines Agency or Food and Drug Administration - have published recommendations on bioanalytical method validation. In its theoretical part, this dissertation deals with description of Alzheimer's dementia with special focus on treatment strategies. Further attention is paid to topics that are directly related to the experimental work - liquid chromatography, mass spectrometry, sample preparation, method validation and pharmacokinetics. The experimental part - a commentary on the author's published articles - consists of three units: I. bioanalytical evaluation of PC-37 and PC-48 - novel 7-methoxytacrine and donepezil-derived dual cholinesterase inhibitors, II. study of the transport of donepezil across the blood-brain barrier with focus on its structure and substructures and III. bioanalytical evaluation of S-K1025 and S-K1026 - new 7-methoxytacrine and tryptophan-derived dual cholinesterase...
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The use of HPLC in the field of chiral separations IV.
Daněk, Alois ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Alois Daněk Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title of thesis: The employment of HPLC in the field od chiral separations IV. The requirements for the quality and safety of medicines are constantly growing at present. Drugs are often chiral substances. Therefore, the importance of chiral separations is increasing. Direct separations using chiral stationary phases are the most used in this field. Silica gel, which is most often used as a carrier for chiral selectors, may contain metal impurities on its surface, which may negatively affect the separation process. This thesis focuses on testing the influence of chromatographic conditions on chiral and achiral interactions of nine selected analytes with the stationary phase. A column with β-cyclodextrin as chiral selector was used for the testing.
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GC analysis of drugs with utilization of ionic liquid as a stationary phase I
Bärová, Karolína ; Kastner, Petr (advisor) ; Kučera, Radim (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Supervisor: PharmDr. Petr Kastner, Ph.D. Student: Karolína Bärová Title of Thesis: GC analysis of drugs with utilization of ionic liquid as a stationary phase I In this thesis, we focused on testing of three commercially obtainable columns with ionic liquids as stationary phases, which we tested on a model sample of ibuprofen and its four pharmacopoeial impurities after derivatization by alkylchloroformates. The results obtained on these columns were compared to results obtained on column with conventional nonpolar stationary phase. Furthermore, we tried to describe and explain retention mechanisms, which were important in these separations, we also tried to optimize methods for our individual columns and extract our derivatives into a nonpolar phase, with the view to diminishing the harmful effect of samples on columns. We appraise the results obtained on ionic liquid stationary phases and on a nonpolar stationary phase as quite comparable. The analysis of our derived samples can be performed on all tested ionic liquid columns and the analysis can be optimized for all of them. Apart from the change in selectivity on the most polar stationary phase, we did not notice any great...
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Nanofiltration
Heidrová, Hana ; Kučera, Radim (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Nanofiltration Diploma thesis Candidate: Hana Heidrová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: PharmDr. Tomáš Holas, Ph.D. Nanofiltration is a pressure-driven membrane process which is characterized by using semipermeable membranes with approximately 1 nm pores. This method is used abundantly for the separation of substances with low molecular weight. It is used for example in the process of product isolation in pharmaceutical industry. This diploma thesis is focused on the description of the behaviour of three commercially produced nanofiltration membranes and also on testing of their potential use in the production of ergot alkaloids. The theoretical part is focused especially on the description of pressure-driven membrane processes, the use of nanofiltration in various areas and also on current and historical use of ergot alkaloids in therapy and on the description of their properties. The practical part is oriented particularly on examination of effect of various experimental parameters on the retention of selected ergot alkaloids (primarily of lysergic and isolysergic acid). The results are compared and critically analysed. Keywords: pressure-driven...
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GC analysis of drugs using ionic liquid as stationary phase II
Hungerová, Lenka ; Kastner, Petr (advisor) ; Kučera, Radim (referee)
Charles university in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Supervisor: PharmDr. Petr Kastner, Ph.D. Student: Lenka Hungerová Title of thesis: GC analysis of drugs using ionic liquid as a stationary phase II This thesis dealt with analysis of ibuprofen and its four pharmacopoeial impurities samples after derivatization by alkylchloroformates by gas chromatography (GC). The thesis builds on a thesis by Karolína Bärová (2018), who tested these samples on one column with a nonpolar stationary phase and on three columns with ionic liquid as a polar stationary phase. Three other columns with ionic liquids were used in this thesis, which showed higher polarity than the columns used by K. Bärová. There was an effort to describe the retention mechanisms, that were manifested here, and to optimize the conditions of the method on all the three columns. Following the previous experiments other options for improvement of the extraction yield of the derivatives into a nonpolar solvent were tested. The results indicate that all the three columns with ionic liquid as stationary phase can be used for analysis of these samples. The conditions of the method were optimized enough on all the columns. The extraction yield into the nonpolar...
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Factors which affect the purification and stability bioconjugates azaftalocyanines
Cichý, Jakub ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Rigorous thesis Factors which affect the purification and stability bioconjugates azaftalocyanines Mgr. Jakub Cichý Charles University, Faculty of Pharmacy in Hradci Králové, Department of Pharmaceutical chemistry and pharmaceutical analysis This work continues in diploma thesis Purification azaphthalocyanines bioconjugates using SPE. It deals with the stability of molecular probes (i.e. "mono" and "dual- labeled") after dilution and storage in a given time period (fridge/freezer). We focused on the content changes of free oligonucleotide chains and probes containing azaphthalocyanine dyes using HPLC with detection at 260 and 673 nm, at following time intervals 0 h, 14 h, 13 days and 33 days. We found that molecular AzaPc probes were stable without significant changes in their content and purity even after a month of storage. The biggest influence on the purity of the azaphthalocyanine bioconjugates had the evaporation metod of the mobile phase from the sample after the purification step. Furthermore, we studied the posibility of purification of the "dual-labeled" probes containing AzaPc by SPE. Unfortunatly, the result showed that the examined SPE cartridges were unable to separate successfully the "mono-labeled" the"dual-labeled" probes from each other. Nevertheless, the phenyl column DSC-Ph (500...
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Non-silica based materials in drug analysis III.
Jiřičková, Nina ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Non-silica based materials in the drug analysis III. Diploma thesis Nina Brejchová
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Sample preparation prior to an essay plays a key role in the drug analysis. Example of a widely used sample preparation technique is a Solid Phase Extraction. This method is characterised by high selectivity, which is given by the type of used sorbent. The aim of this thesis is to study the application of a new sorbent in Solid phase extraction which is zirconium oxide modified by graphene. Graphene is an allotropic modification of carbon possessing a specific adsorptive properties. Therefore it can be used besides other areas in chemical analysis. This thesis focuses on the testing on adsorptive capability of this sorbent using a mixture of model basic drugs. The attention was also paid to pH of solution used for conditioning of the sorbent and type of eluents. After the extraction, the samples were analysed by high- performance liquid chromatography, using a gradient elution. The most appropriate extraction environment was aqueous environment. Extraction recoveries obtained with the prepared sorbent were compared to those obtained with silica gel. The highest recoveries were obtained by extraction of...
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