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Development and metrological evaluation of gas chromatographic methods for quality and safety control of alcoholic products
Korban, Anton ; Čabala, Radomír (advisor) ; Kubinec, Róbert (referee) ; Maier, Vítězslav (referee)
Dissertation is dealing with the development of methods of quality control of alcoholic products, particularly, with quantification of volatile congeners. Previously suggested "Ethanol as internal standard (IS)" method was compared with existing analytical methods of internal and external standardisation. After satisfactory results the method was validated in one laboratory and then an inter-laboratory study which included nine laboratories from four countries was conducted. It was shown that the method usage on GC-FID is beneficial due to the absence of necessity of internal standard compound addition into tested sample, and absence of tedious sample alcohol by volume (ABV) or density measurements. The algorithm of the method usage on GC-MS instruments was also suggested and developed. It was found out that MS detector sensitivity should be reduced in order to register ethanol signal successfully. For this aim it was suggested to employ less abundant 47 m/z ions during ethanol elution. These ions correspond to non-fragmented ethanol molecules containing one heavy isotope, mainly 13 C. According to the obtained results the suggested methodology allowed employing the "Ethanol as IS" method on GC-MS instruments with metrological properties better or similar as for the traditional IS method. The...
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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...
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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...
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