|
|
The development of new methods of ultra-high performance supercritical fluid chromatography for pharmaceutical applications
Plachká, Kateřina ; Nováková, Lucie (advisor) ; Kučera, Radim (referee) ; Novák, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Mgr. Kateřina Plachká Supervisor: prof. Pharm.Dr. Lucie Nováková, Ph.D. Title of Doctoral Thesis: The development of new methods of ultra-high performance supercritical fluid chromatography for pharmaceutical applications A compilation of seven articles and three book chapters dealing with the applicability of supercritical fluid chromatography (SFC) methods in the field of pharmaceutical analysis is presented in this dissertation thesis. The first part focuses on pharmaceutical quality control and especially impurity control. The presented articles are dealing with the searching for generic screening approach for the development of SFC methods and with the subsequent optimization and validation of these methods. The screening conditions were compared based on developed mathematical model. The generic combination of diol stationary phase and 0.1 % ammonium hydroxide in methanol as modifier of CO2-based mobile phase was proposed as a starting point for SFC method development based on the obtained results. Several challenges were described during optimization of UHPSFC methods and their solution was proposed. The benefits of acetonitrile added to the modifier, advantages of column coupling and the...
|
|
|
Non-silica based materials in drug analysis IV.
Ženíšková, Tereza ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Non-silica based materials in drug analysis IV. Diploma thesis Tereza Ženíšková Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Heyrovského 1203, Hradec Králové. Sample preparation is an important step before the analysis itself. It enables removal of the ballast components, which could interfere with an analyte or even disable the analysis. Solid phase extraction (SPE) belongs among the most popular sample preparation techniques. Silica is the most often used sorbent for SPE, however new, more durable sorbents with different selectivity have appeared. This thesis focuses on employment of zirconium dioxide and its ability to retain analytes having Lewis base character via ligand exchange. We tested to use zirconium dioxide in extraction of indomethacin as a Lewis base from suppositories. The influence of conditioning solvents with different polarity and extractions solvents was investigated. 10% acetonitrile in methylene chloride was found to be the best solvent for conditioning of zirconia. Methanolic ammonia solution was used as eluent. After some experiments the concentration and the volume of the eluent was set at 0.25M NH3 in MeOH and 3 mL. Diclofenac was used as the internal standard. The recovery for sorbent after...
|
|
|
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...
|
|
|
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...
|
|
|
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,...
|
|
|
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...
|
|
|
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.
|
|
|
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...
|
|
|
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...
|
|
|
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...
|
guest ::
RSS feed.