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Development of the UHPLC-PDA method to determine the active substances in the tablet Ataralgin
Chocová, Natálie ; Kozlík, Petr (advisor) ; Hraníček, Jakub (referee)
The Ataralgin tablet is an over-the-counter drug that helps against pain and elevated body temperature. The tablet contains three active substances - paracetamol, caffeine and guaifenesin. The aim of this thesis was to develop a rapid, effective, selective and simple UHPLC-PDA method suitable for the determination of active substances in the Ataralgin tablet which would subsequently serve for quality control during the production of this drug in the pharmaceutical industry. Separation was performed on the Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 µm), the column temperature was set at 40 řC, autosampler temperature was 10 řC, the mobile phase was composed of methanol (B) and distilled water with the addition of 0.1% formic acid (A), sample injection volume was 1 µl and the flow of mobile phase was 0.4 ml·min-1 , gradient elution (time: 0-0.5-1.5-2.5-3-5.5 min, A: 85-85-30-30- 85-85% v/v). UV detection at 275 nm and the total analysis time was 5.5 minutes. The trueness (relative error) was in the range of 0.05 - 2.73 % and the accuracy (relative standard deviation) was in the range of 2.38 - 5.79 %. The LOD values were: 9.25·10- 4 mg·ml-1 for paracetamol, 2.15·10-4 mg·ml-1 for caffeine and 7.93·10- 4 mg·ml-1 for guaifenesin and values for the LOQ were 3.08·10-3 mg·ml-1 for paracetamol, 7.17·10-4...
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Circadian clock and detoxication processes in the liver
Ludvíková, Tereza ; Pačesová, Dominika (advisor) ; Kolář, David (referee)
The circadian system influences almost all physiological processes in the mammalian body. Among other things, detoxication processes in the liver are under circadian control. Both central and peripheral clock in the liver regulate the expression of genes involved in the detoxication of xenobiotic substances and drugs. The first part of this thesis summarizes the main characteristics of the central and peripheral circadian clocks, including their molecular basis. The second part focuses on the main functions of liver tissue with a focus on detoxification processes. The emphasis of the third section is on circadian rhythms in the expression and activity of enzymes called cytochromes P450, which are the most important system catalyzing phase I detoxication, and also briefly discusses the influence of the circadian system on the expression of nuclear receptors and PAR bZIP transcription factors involved in the regulation of cytochrome P450 transcription. The last section describes the influence of the circadian system on the efficacy and toxicity of selected drugs, on paracetamol metabolism with the main purpose of describing how paracetamol-induced hepatotoxicity is affected by time of administration. Key words: circadian system, liver, detoxication, cytochrome, paracetamol
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Oxidative degradation of paracetamol
Tůmová, Michaela ; Křížek, Tomáš (advisor) ; Kozlík, Petr (referee)
Paracetamol is a commonly used drug for newborn babies against increased physical temperature and pain. Therefore, it is necessary to determine the stability of this drug, which is an important factor for its safety and efficiency. One of the methods for determining the stability of drugs is the identification of their degradation products. This bachelor thesis is about the development and optimization of ultra high performance liquid chromatography method for determining paracetamol degradation products, which are formed by chemical or electrochemical oxidative degradation. A column UPLC CSH PHENYL-HEXYL (1,7 μm, 100 × 2,1 mm) was chosen as optimal for this separation. Furthermore, the aqueous component of the mobile phase was a 20 mM ammonium acetate solution, and the organic component was methanol. After optimization, a partial validation of the method was performed, during which the linear dynamic range, the limit of detection, the limit of quantification, repeatability of retention time and peak area, and recovery were evaluated. Chemical and electrochemical oxidative degradation was performed for paracetamol solution with a concentration of 1 mg/ml. Additionally, chemical degradation was performed with the addition of hydrogen peroxide with a concentration of 0,5 % and 3 % at a temperature of...
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Awareness of the risk of paracetamol intoxication in the lay and professional population
HAVELKOVÁ, Barbora
The bachelor's thesis addresses awareness of the risks of paracetamol intoxication in the lay and professional population. Paracetamol is a very popular over-the-market drug. However, few are aware of the risks associated with improper use. At the same time, the thesis examines the knowledge and opinions of general nurses in the area of proper use of drugs containing paracetamol, the education of patients, and increasing competencies in the prescription of over-the-counter drugs. The theoretical part describes the issue of paracetamol intoxication, the group of drugs in which paracetamol is found, and, last but not least, the increase in competencies of the aforementioned prescription of over-the-market drugs, both in the Czech Republic and abroad. The objectives of the thesis were achieved by combining quantitative and qualitative research surveys. The quantitative investigation was carried out in the form of online questionnaires intended for the public. The qualitative investigation conducted a semi-structured interview with nurses working both in the hospital and in the ambulate sphere. The semi-structured interview mapped nurses' knowledge of the risks of paracetamol intoxication and views on increasing competencies in prescribing free medications. The results of the research survey show that the professional population (nurses) are oriented towards the risks of intoxication with paracetamol. Although the lay population does not know the recommended maximum daily dose of paracetamol, it knows the drugs that contain paracetamol.
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ANALYSIS OF COMPETITION ON THE CONSUMER'S MARKET WITH SELECTED COMMODITY
VALDMANOVÁ, Markéta
I have used comparison of gathered data from Consumers Defence Association (Sdružení obrany spotřebitelů) and own market research for my Thesis to analyze the market from the consumer{\crq}s perspective in terms of possibility to choose medicaments. Porter{\crq}s model of Five Forces was additionally helpful to examine the competitive environment in the market. I tried to analyze the market from the consumer{\crq}s defence perspective in the Conclusion. After evaluation of these above mentioned analyses I came to conclusion that the competition between Panadol and Paralen consists in particular in price. The informants have also stated that they buy the ``painkillers{\crqq} on grounds of previous good experience or on their doctor{\crq}s recommendation. Another possibility how to compete in the market is availability of a pharmacy, price, staff willingness, and assortment range. The reasons that could threaten Panadol and Paralen, is a huge market share of Ibalgin; in general the pharmaceuticals market is endangered by enter of generic drugs and possibility to buy drugs in other places than at the chemist{\crq}s. From perspective of the consumers defence, the competitive environment has certain problems. It is in particular impossibility to purchase drugs outside of the pharmacy, markedly non-transparent financing system and problems with determination of reimbursement from health insurance companies.
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Use of liquid chromatography in pharmaceutical analysis and preparation of monolithic stationary phases for thin-layer chromatography
Vojta, Jiří ; Coufal, Pavel (advisor) ; Tůma, Petr (referee) ; Jelínek, Ivan (referee)
(EN) In the first part of this work, analytical methods for determination of impurities of active pharmaceutical ingredients (API) in combined pharmaceutical dosage forms were developed and validated. Development of the methods covered both the optimization of sample preparation procedure and chromatographic conditions. The methods were validated according to International Conference on Harmonization guideline and both of them were confirmed to be able to analyze stability samples. Impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fourth API fenpiverinium bromide were separated by using ion-pair reversed phase chromatography with gradient elution. Symmetry C18, 250 x 4,6 mm, 5 µm heated to 35 řC was used as a separation column. A diode array detector was used. The detection wavelengths were set as follows: 220 nm for paracetamol impurity K, 245 nm for paracetamol and its other impurities and 285 nm for codeine, pitophenone and their impurities. Impurities in valsartan, amlodipine besylate and hydrochlorothiazide were separated by reversed phase UHPLC method with gradient elution. Chromatographic column Zorbax Eclipse C8 RRHD, 100 x 3,0 mm, 1,8 µm heated to 30 řC and spectrophotometric detection were used. The detection wavelengths were set as...
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Pharmacological perspectives and clinical benefits of SIRT1 and AMPK activators and inhibitors in inflammatory and oxidative stress in the liver
Njeka Wojnarová, Lea ; Kutinová Canová, Nikolina (advisor) ; Hodek, Petr (referee) ; Votava, Martin (referee)
Introduction: Liver diseases represent a significant cause of morbidity and mortality worldwide. Previous experimental studies have shown that polyphenolic compound, resveratrol, as a less specific activator of sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) can effectively attenuate acute liver injury. Although SIRT1 and AMPK have been widely studied for many years, further evidence for a mutual SIRT1/AMPK signaling mechanism and how it is modulated by drugs of small molecules had not been fully clarified at start of our experimental work. Goal: The main objective of the presented research was to investigate the relationship of SIRT1 and AMPK in process of hepatotoxicity/hepatoprotection in in vivo and in vitro animal model of acute drug-induced liver injury. Methods: Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by a single dose of D-Galactosamine (GalN)/lipopolysaccharide (LPS) or acetaminophen (APAP). Some rats and cultured hepatocytes were treated by resveratrol, synthetic selective activator or inhibitor of SIRT1 and AMPK. Biochemical markers of liver injury (aminotransaminases, total bilirubin), oxidative stress (nitrites) and lipid peroxidation (conjugated dienes, TBARS) were measured in the plasma, medium or liver homogenate. Liver...
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Use of liquid chromatography in pharmaceutical analysis and preparation of monolithic stationary phases for thin-layer chromatography
Vojta, Jiří
(EN) In the first part of this work, analytical methods for determination of impurities of active pharmaceutical ingredients (API) in combined pharmaceutical dosage forms were developed and validated. Development of the methods covered both the optimization of sample preparation procedure and chromatographic conditions. The methods were validated according to International Conference on Harmonization guideline and both of them were confirmed to be able to analyze stability samples. Impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fourth API fenpiverinium bromide were separated by using ion-pair reversed phase chromatography with gradient elution. Symmetry C18, 250 x 4,6 mm, 5 µm heated to 35 řC was used as a separation column. A diode array detector was used. The detection wavelengths were set as follows: 220 nm for paracetamol impurity K, 245 nm for paracetamol and its other impurities and 285 nm for codeine, pitophenone and their impurities. Impurities in valsartan, amlodipine besylate and hydrochlorothiazide were separated by reversed phase UHPLC method with gradient elution. Chromatographic column Zorbax Eclipse C8 RRHD, 100 x 3,0 mm, 1,8 µm heated to 30 řC and spectrophotometric detection were used. The detection wavelengths were set as...
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