National Repository of Grey Literature 197 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
LC-MS/MS study of phase one in vitro biotransformation of potential drugs against Alzheimer's disease
Kuřátková, Aneta ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
No treatment that would completely stop the progression of Alzheimer's disease has not been found yet. Recently used tacrine showed good results in the treatment of Alzheimer's disease, however long-term use led to chronic hepatotoxicity due to its metabolites. This master thesis deals with the compound 7-phenoxytacrine, one of the promising tacrine derivatives, which is one of the candidates for potential use in the therapy of Alzheimer's disease. Due to the formation of hepatotoxic metabolites of tacrine after the biotransformation in human liver, it appears necessary to identify the emerging metabolites of 7-phenoxytacrine molecule. Within this master's thesis in vitro biotransformation study of 7-phenoxytacrine using human liver microsomes was performed. High performance liquid chromatography with tandem mass spectrometry was used to determine the parent substance and the seventeen 7-phenoxytacrine metabolites. The analytical method showed the formation of six monohydroxylated and eleven dehydroxylated metabolites of 7-phenoxytacrine. Thus, we concluded that hydroxylation is the major metabolic reaction after in vitro microsomal biotransformation. In addition to the identification of metabolites, a quantification and microsomal stability study, including the determination of the amount of...
Validation of chromatographic methods in pharmaceutical analysis
Kegkeroglou, Iokasti ; Kučera, Radim (advisor) ; Kastner, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Iokasti Kegkeroglou Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title of Thesis: Validation of chromatographic methods in pharmaceutical analysis Validation is an integral part of every analytical method. Its aim is to demonstrate that the method is suitable for the intended use. This work provides an overview and comparison of documents related to the validation of bioanalytical methods. The work includes guidelines that are currently valid in Europe, the USA or have general validity. At first, attention is paid to the history and developments in this area. Subsequently, the parameters that need to be tested in the validation study are described and are divided according to the regulatory authorities. The following chapter compares the latest versions of the guidelines regarding the validation of separation bioanalytical methods issued by the EMA, FDA, and ICH. Although the individual methodologies are similar in many aspects, there are still differences among them. Hopefully, the differences will be eliminated in the framework of harmonization and only one methodological guideline could be used worldwide. Finally, it follows a detailed statistical evaluation of...
HPLC evaluation of tyrosine and its metabolites
Michailellis, Panagiotis ; Kastner, Petr (advisor) ; Kučera, Radim (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Panagiotis Michailellis Supervisor: PharmDr. Petr Kastner, PhD. Title of Diploma Thesis: HPLC evaluation of tyrosine and its metabolites Tyrosine is an important precursor of catecholamines, which are dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). These are neurotransmitters and hormones, crucial for every living organism. Therefore, their identification and evaluation in biological material would aim to understand their function and behavior more accurately. This Diploma Thesis is a review on how to evaluate catecholamines and their metabolites in biological matter with analytical methods used in Pharmaceutical Analysis, especially with HPLC. First chapters present theoretical knowledge about metabolism of tyrosine and its metabolites, how a sample from an organism should be treated in order to be examined, information about HPLC, CE, GC apparatuses and the main detectors used in analysis of these compounds. In literature review, tables are presented, concerning different sample preparation methods, HPLC details and characteristics, and finally a sum of all the analytical methods studied for this Diploma Thesis. All the articles and...
Development of LC-MS method for determination of selected endocrine disruptors
Chvalkovská, Eliška ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Charles University Phaculty od Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Eliška Chvalkovská Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Martin Novák Title of thesis: Development of LC-MS method for determination of selected endocrine disruptors The thesis is focused on the development and optimization of LC-MS method for the determination of twelve endocrine disruptors in amniotic fluid of pregnant women in the third trimestr of pregnancy. There is a suspision that premature births are connected with an increased incidence of endocrine disruptors in amniotic fluid. The analytes were extracted by liquid-liqud extraction with 4-methylpentan-2- on. The analytical method is based on using reverse phase high-performance liquid chromatography with Hypersil C4 GOLD column (2.1 × 100 mm, particles 1.9 µm). For analysis the gradient elution with the mobile phase A (0.5% (v/v) formic acid aqueous solution) and B (0.5% (v/v) formic acid solution in acetonitrile) at a flow rate of 0.5 ml/min, injection 5 µl and column oven temperature 35 řC was used. The high- resolution mass spectrometer Orbitrap Q Exative Plus with atmospheric pressure chemical ionization in positive mode was used to identify and determine the response of...
Optimization of derivatization reaction conditions for GC-MS analysis of selected compounds
Jan, Tomáš ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Candidate: Tomáš Jan Title of Thesis: Optimization of derivatization reaction conditions for GC-MS analysis of selected compounds Quinolinic acid is an endogenous molecule, downstream product of the kynurenine pathway, through which the amino acid L-tryptophane is metabolised. Quinolinic acid acts as an agonist at the NMDA receptor. Overactivity of this receptor leads to the cell death of neurons. Current research shows the connection between a high level of quinolinic acid and a higher risk of neurodegenerative diseases development and behavioural disorders. The level can be increased by the excessive intake of tryptophane (e.g. food supplements declaring calming effect and mental health support) or ongoing inflammation in the organism. The current work deals with the development of an analytical method for the determination of quinolinic acid in various biological matrices using GC/MS and complements methods analysing other metabolites of tryptophan. Derivatization by alkyl chloroformate was met with success. The selectivity was compared on column RTX-5MS containing non-polar stationary phase and polar column SLB-IL59 using ion...
The uset of HPLC in the field of chiral separations VII.
Štilcová, Kristýna ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Kristýna Štilcová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Ondřej Horáček Title of Thesis: The employment of HPLC in the field of chiral separations VII. Boron clusters are inorganic, synthetically prepared, three-dimensional, cage-like structures. Boron cluster compounds which are made only of boron and hydrogen atoms are completely symmetrical. Their symmetry can be disrupted by endo- or exoskeletal substitution resulting in chiral compounds. Carboranes, subgroup of the boron cluster compounds, contain at least one carbon atom in their structure and usually include exoskeletal substitution. Therefore, the metallacarboranes containing cobalt bis(dicarbollides) and 7,8-dicarba-nido-undecaborates that have been studied can be found among these chiral structures. Thanks to the specific properties such as high lipophilicity, metabolic stability and delocalized negative charge, the studied compounds can be used as isosteric substitution of phenyl ring in pharmacophores. Due to the growing interest in cobalt bis(dicarbollides) and 7,8-dicarba-nido-undecaborates and the importance of chirality in pharmacy, suitable conditions for chiral...
UHPLC-HRMS analysis of cannabinoids in biological matrix
Ocelková, Anna ; Kučera, Radim (advisor) ; Bavlovič Piskáčková, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: RNDr. Martin Mžik, Ph.D. Candidate: Bc. Anna Ocelková Title of Thesis: UHPLC-HRMS analysis of canabinoids in biological matrix Cannabis is still considered to be the most widespread drug worldwide. The main molecule responsible for its effects is psychotropic cannabinoid Δ9 -tetrahydrocannabinol, which is converted into active metabolite 11-OH-Δ9 -THC and inactive metabolite 11-nor-9-carboxy-Δ9 -THC in the human body. The determination of these three molecules in human serum is one of the basic analytical assays that are performed in toxicological laboratories, as it reflects the state of current drug exposure. Another cannabinoid - cannabidiol (CBD) - is also gaining worldwide awareness, and its therapeutic effects have been the subject of many clinical studies. CBD has no psychoactive effect and its potential for the treatment of a wide range of diseases was first fully acknowledged with the launch of the first drug (Epidiolex®) on the US market in 2018 with CBD being the main active ingredient. The aim of this thesis is development and validation of the sensitive method for determination of Δ9 -THC,11-OH-Δ9 -THC, Δ9...
Chiral separation of boron cluster compounds
Linková, Kristýna ; Kučera, Radim (advisor) ; Lochman, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Kristýna Linková Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Ondřej Horáček Title of thesis: Chiral separation of boron cluster compounds The boron atom has the ability to form electro-deficientient bonds, when only two electrons participate in the three bonds. Significant delocalization of electrons over the three- center bond is responsible for the formation of three-dimensional clusters. Boron cluster compounds have an abiotic character. They are characterized by their specific properties, such as thermal and metabolic stability, high lipophilicity and delocalized negative charge. These compounds are investigated as isosteric to phenyl group in the field of medicinal chemistry. They have anti-cancer activity, the ability to inhibit HIV-proteases and anti-rheumatoid activity. Furthermore, boron cluster compounds have been used in neutron capture therapy in the treatment of cancer. Some boron cluster compounds studied as new potential drugs are chiral, therefore it is necessary to get enantiomerically pure substances to further expand their use in pharmacy and medicine. The recent investigations in our research group have been focused on the...
The employment of HPLC for separation of bioconjugates of azaphtalocyanines
Kaminská, Marta ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Diploma thesis The employment of HPLC for separation of bioconjugates of azaphtalocyanines Marta Kaminská Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control This diploma thesis deals with development of suitable chromatographic conditions for separation of bio-conjugates of azaphthalocyanines. These compounds are of great interest today, they might be useful as potential quenchers of fluorescence in molecular probes. The experiments were carried out in analytical and semi-preparative scale. Nine C18 chromatographic columns were tested. The conditions for analytical and semi-preparative chromatography were optimized. The following chromatographic conditions for separation of bio-conjugates of azaphtalocyanines were found (analytical method):  Stationary phase : Hypersil BDS, 100 × 4,6 mm, 3 μm particle size  Mobile phase A : 50 mM water solution TEAA in 12 % acetonitrile;  Mobile phase B : acetonitrile;  Gradient elution.  Other conditions : column temperature 40 řC, flow rate 1 ml per minute  Detection 254 nm, 374 nm, 552 nm, 673 nm The following chromatographic conditions for separation of bio-conjugates of azaphtalocyanines were found (semi-preparative method) :  Stationary phase : Hypersil BDS 250 × 4,6 mm, 5 μm...
LC-HRMS analysis of selected drugs in biological material II.
Švarcová, Kristýna ; Kučera, Radim (advisor) ; Bavlovič Piskáčková, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Kristýna Švarcová Consultant: RNDr. Martin Mžik, Ph.D. Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title: LC-HRMS analysis of selected drugs in biological material II. Anxiety disorders affect up to 25 % of the population in their life, the lifetime prevalence is 13,6 %. Insomnia affect at least one third of the population in their life, the prevalence is 15-40 %. Drugs used to treat anxiety and insomnia easily cross the blood-brain barrier and affect the CNS. It is therefore necessary to determine the correct dosing schedule and monitor treatment. The result is optimization of treatment, reduction of side effects and increased patient adherence to treatment. The rapid qualitative and quantitative analysis for urgent cases of intoxication is also needed. This diploma thesis deals with development and optimization of an extraction method for selected benzodiazepines (alprazolam, bromazepam, diazepam, chlordiazepoxide, clonazepam, midazolam, oxazepam) and zolpidem in human serum. Subsequently, the whole analytical method was validated for use in clinical practice using the UHPLC-HRMS. Protein precipitation with acetonitrile was the most suitable sample preparation...

National Repository of Grey Literature : 197 records found   1 - 10nextend  jump to record:
See also: similar author names
1 KUČERA, Richard
7 Kučera, Radek
4 Kučera, Roman
1 Kučera, Rostislav
3 Kučera, Rudolf
Interested in being notified about new results for this query?
Subscribe to the RSS feed.