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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...
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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...
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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...
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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...
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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...
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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...
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Modification of the capillary wall for the separation purpose I.
Blažková, Andrea ; Kučera, Radim (advisor) ; Kastner, Petr (referee)
Department of Pharmaceutical Chemistry and Drug Analysis Andrea Opavská doc. PharmDr. Radim Kučera, Ph.D. Modification of the capillary wall for the separation purpose I In general, capillary electrophoresis is a separation method suitable for the analysis of charged molecules, eventually neutral substances. The interest in this method and its further modification (e.g. capillary electrochromatography) has been increasing in recent years, is developing. In the case of capillary electrochromatography, the development focuses mainly on the modification of the inner wall of the capillary. The purpose of this modification is in particular to introduce a stationary phase that would improve selectivity, as well as the modification of the electroosmotic flow. The thesis deals with the modification of the internal capillary wall and the subsequent testing of the prepared capillary. One possibility is chemical coating. The second tested method is called Layer-by-Layer and represents the layering of variously charged substances in layers interacting with each other through electrostatic forces. In our work we used polycation poly(diallyldimethylammonium chloride) and graphene dispersion. The choice of graphene is very advantageous because it has excellent adsorption properties due to its morphological...
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Employment of gas chromatography in the field of drug analysis III.
Šináklová, Barbora ; Kučera, Radim (advisor) ; Vrbatová, Ivana (referee)
Diploma thesis Employment of gas chromatography in the field of drug analysis III. Barbora Šináklová Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control The gas chromatography represents a sensitive analytic method. Effective and fast separation of complicated compounds and manipulation with small amounts of samples using a relatively simple equipment characterise the GC method in particular. Butan-1,3-diol is a substance used in chemical industry as a solvent and a carrier of aromatic substances, or for plastics and explosives production. It is added to antifreeze mixtures in radiatores. Another usage possibility constitute cosmetic products, the substance also occurs in pesticides. Because of its antimicrobial effects, butan-1,3-diol is added to cleansing articles. It extends the effect of certain syringe articles and increases the effect of dissolved effective substances. This method was used in this diploma thesis to determine the volume of butan-1,3-diol and the method was validated. The work was realized with gas chromatograph Shimadzu GC-2010 with flame- ionization detector. Hydrogen was chosen as the carrier gas. Supelcowax TM-10, Fused silica capillary column, 30 m × 0,53 mm × 0,5 µm was used. The inner standard...
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The employment of HPLC in the field of drug analysis IV.
Krejčí, Tereza ; Kučera, Radim (advisor) ; Kovaříková, Petra (referee)
Employment of HPLC in the field of drug analysis IV. Diploma thesis Tereza Krejčí Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control Heyrovského 1203, Hradec Králové. The diploma thesis is targeted to usage of High Performance Liquid Chromatography in the field of Quality control of drug substances. Methylergometrine is a derivative of ergometrine that belongs to Ergot alkaloids. These native origin substances have strong pharmacological effects on different human body systems already in low concentrations. Active components from ergot are acquired by extraction and subsequent separation of individual components from a mixture. These substances are repurified. It is very expensive to produce totally pure substances and thus final substances may contain defined amount of impurities. In case of methylergometrine Related substances are analysed according to the valid European pharmacopoeia. Nine substances are in the specification of possible analysed components, tenth component (-)methylergometrinine has not been described in the pharmacopoeia so far. This thesis deals with development of chromatographic conditions for qualitative separation of a mixture of methylergometrine and its impurities on zirconia based stationary...
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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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