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Problems of stability testing of the active substances and pharmaceutical preparations using HPLC
Havlíková, Lucie ; Solich, Petr (advisor) ; Jokl, Vladimír (referee) ; Sochor, Jaroslav (referee)
"Problems of Stability Testing of the Active Substances and Pharmaceutical Preparations Using HPLC" The presented thesis deals with using of high performance liquid chromatography for the analysis of pharmaceutical active substance, its degradation products, and impurities in pharmaceutical preparations. The theoretical part describes in a more detailed way the topic stability and impurity testing in pharmaceutical preparations. The HPLC theory, method optimization, isolation procedures, method validation, HPLC/MS, and UPLC are characterized briefly in separate chapters. The practical part of the thesis focuses mainly on the development and validation of new chromatographic methods for simultaneous determination of active substances, impurities, and preservatives in topical pharmaceutical preparations. Six original methods, which are used for the quality control and stability testing of pharmaceuticals, were developed and validated. The active substance indomethacin and two degradation products (5-methoxy-2- methylindoleacetic acid and 4-chlorobenzoic acid) were monitored in antiflogistic topical preparation Indomethacin gel (see attachment 5.2). For antimycotically active topical preparation Terbinafin cream, method for determination of the active substance terbinafine hydrochloride, degradation...
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Versatile use of liquid chromatography and mass spectrometry in drug metabolism studies
Suchanová, Bohumila ; Wsól, Vladimír (advisor) ; Solich, Petr (referee) ; Lemr, Karel (referee)
Human organism has always been exposed to a vast array of chemicals encountered in the environment. Chemical revolution has significantly influenced biological evolution of humans leading to serious unpredictable toxicities. In response to continual chemical stress they have developed a variety of enzymes to transform these xenobiotics. Xenobiotics are mostly highly lipophilic and cannot readily be excreted from the body without metabolism to more hydrophilic, water-soluble metabolites. Not only environmental chemicals represent xenobiotics but also drugs, dietary components etc. Biotransformation studies play an important role in the drug discovery and development process. Usually data from drug metabolism is required before a new substance can advance towards the development stages of a new therapeutic agent. Data on metabolism is frequently used to optimize drug candidates, suggest more active compounds or support toxicology studies. The increased flux of new chemical entities into drug discovery has placed an increased need for fast and reliable information on the metabolism of these substances. Liquid chromatography coupled with mass spectrometry can meet demands for rapid drugs and metabolites analysis imposed by modern drug discovery strategies. This dissertation thesis presents an evidence...
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Application of Sequential injection analysis in pharmaceutical analysis
Klimundová, Jana ; Solich, Petr (advisor) ; Blešová, Marie (referee) ; Karlíček, Rolf (referee)
SSUUMMMMAARRYY IINN EENNGGLLIISSHH This work is concerned on sequential injection analysis and its use in the field of pharmaceutical analysis. This flow method is a versatile, multi-purpose analytical system and for this is gaining more popularity in analytical chemistry. Firstly the review based on pharmaceutical applications was published. The new enhanced techniques such lab-on-valve, micro-SIA, bead injection and sequential injection chromatography was discussed. The experimental part is focused on the use of SIA for automation of long- lasting processes monitoring in pharmaceutical methods of analysis. Fully automated system for in vitro release testing of semisolid dosage forms was established. This test was based on Franz diffusion cell and its connection with SIA system. The system was tested for monitoring release profiles of three commercial preparations containing salicylic acid (Belosalic, Diprosalic, Triamcinolon S). The release profiles were statistically compared. The native fluorescence of salicylic acid was used for fluorimetric detection. Phosphate buffer pH 7.4 was the receptor medium, different membranes were tested. Samples were taken at 10 min intervals during 6 hours of the release test and each test was followed by calibration with five standard solutions. Other work was based on...
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Development and validation of HPLC method for determination of retinyl esters in human serum using monolithic columns.
Krčmová, Lenka ; Solich, Petr (advisor) ; Šatínský, Dalibor (referee)
DEVELOPMENT AND VALIDATION OF HPLC METHOD FOR DETERMINATION OF RETINYL ESTERS IN HUMAN SERUM USING MONOLITHIC COLUMN Absorption test of vitamin A is used for monitoring of intestinal permeability and may represent a sensitive indicator of intestinal damage. In this study, a simple and rapid reversed- phase high-performance liquid chromatography (RP-HPLC) procedure for selective and sensitive determination of retinol, -tocopherol, retinyl-palmitate and retinyl-stearate in blood serum has been developed and used for the monitoring of intestinal mucosal damage in cancer patients treated with cytotoxic drugs after absorption test of vitamin A. The HPLC instrumentation Series 200 LC from Perkin Elmer (Norwalk, USA) with diode- array detector (DAD) was used for the analysis. Separation of retinol, -tocopherol, retinyl- palmitate and retinyl-stearate were performed using the monolithic column Chromolith Performance RP-18e, 100 x 4.6 mm (Merck, Darmstadt, Germany). The gradient elution was used at the flow rate 3 ml min-1 ; mobile phase methanol:water (95:5) in 0-2.1 min and methanol:2-propanol (60:40) in 2.1-4.9 min. The total time of analysis was 6 min. The injection volume of sample was 20 μl and analysis was done at ambient temperature. The detection of retinol, -tocopherol and retinyl esters was carried out...
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Simultánní stanovení kovových kationů (hořčíku, vápníku a hliníku) v léčivých přípravcích využitím iontově výměnné kapalinové chromatografie a ELS detekce
Spáčil, Zdeněk ; Solich, Petr (advisor) ; Nováková, Lucie (referee)
SOUHRN Magnesium a kalcium hrají esenciální roli v existenci živých organismů. Magnesium, se účastní kolem 300 základních enzymatických reakcí, je důležité pro energetický metabolismus, zastává klíčovou roli v neurotransmisi, při imunitních funkcích a regulaci neuromuskulární aktivity srdce. Kalcium kromě strukturální, elektrofyziologické a intracelulárně regulační funkce je také kofaktorem extracelulárních enzymů a regulačních proteinů. Rovnováha těchto minerálů v těle naplňuje důležitou podmínku potřebnou k udržení zdraví. Jejich nedostatek nebo naopak nadbytek v organismu je spojen s řadou vážných syndromů a onemocnění. Aluminium neplní žádnou fyziologickou funkci, důležité je z hlediska jeho toxikologie. Magnesium, kalcium a aluminium jsou využívány samostatně nebo v kombinaci ve formě různých solí, oxidů, hydroxidů nebo komplexů při výrobě mnoha farmaceutických přípravků nebo potravinových doplňků. Český lékopis 2005 používá ke stanovení magnesia, kalcia a aluminia chelatometrickou titraci edetanem disodným (přímou nebo zpětnou). Další metody užívané k detekci magnesia, kalcia nebo aluminia jsou například ASS, ET-AAS, SIA s UV-VIS detekcí, multikomponentní FIA s detekcí diodovým polem, FIA za iontově selektivní elektrodové detekce, iontově selektivní elektrody, iontová chromatografie s piezoelektrickou...
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