Current sources on the studied issues

Defined in the individual study plan of the doctoral student and in the Study Regulations of FPHARM CU.

The doctoral student will obtain the rating completed with credit value after successfully defending the dissertation thesis. Fulfillment of required conditions according to regulations and submission of dissertation thesis.

Slovak language, in case of the consent of the dean and the consent of the chairman of the commettee of the doctoral study on the proposal of the doctoral student also in another world language, preferably English.

1) The doctoral student will prepare a dissertation thesis. Through the dissertation, the student demonstrates the ability and readiness for independent scientific and creative activity in the field of research or development or for independent theoretical and creative activity. It should be characterized by a high degree of analysis and synthesis of knowledge, as well as a sufficient overview of the existing literature. The work must be original, created by the author in compliance with the rules of working with information sources. The school work must not have the character of plagiarism, nor must it infringe the copyrights of other authors. The author is obliged to thoroughly cite the information sources used, to name the specific and specific research results of other authors or authors, by citing the relevant source, to accurately describe the methods and working procedures of other authors or collectors, to document laboratory results and field research of other authors or collectives. The citation technique is guided by the practice in the given scientific field, respecting the relevant standards and norms. 2) The doctoral student will briefly state the essential content of his / her dissertation, its concept, results and contribution in the defense of the dissertation. 3) The doctoral student will take a position on the opinions of the opponents, in particular he will comment on all objections and comments and answer their questions. 4) During the discussion, the doctoral student will answer all questions and take a stand on all suggestions and objections of its participants.

after a successful defense he / she will obtain a title PhD.

Current sources on the studied issues

Defined in the individual study plan of the doctoral student and in the Study Regulations of FPHARM CU.

The doctoral student will obtain the rating completed with credit value after successfully passing the dissertation exam with the result passed

Slovak language, in case of the consent of the dean and the consent of the chairman of the commettee of the doctoral study on the proposal of the doctoral student also in another world language, preferably English.

1) The dissertation examination consists of a part consisting of a discussion of the written work for the dissertation examination - project proposal.

2) The dissertation examination consists of a part in which the doctoral student has to demonstrate theoretical knowledge in the specified subjects of the dissertation examination.

3) The subjects of the dissertation examination consist of the main subject and secondary subjects according to the characteristics of the study program of the doctoral degree in the field of study.

At the dissertation exam, the student must demonstrate not only knowledge of the specified subjects of the exam, but also the ability under the supervision of the supervisor to submit a dissertation project proposal, method of solving experimental procedures, ability to form conclusions based on results and defend their project proposal before a committee of the doctoral study.

Chackalamannil, S., Rotella, D., & Ward, S. (2017). Comprehensive Medicinal Chemistry III, 3. Vyd. Elsevier, Amsterdam, Holandsko, 4536 s.

Patrick, G.L. (2017). An Introduction to Medicinal Chemistry. 6. Vyd. Oxford University Press, New York, USA, 832 s.

Remko, M. (2019). Základy medicínskej a farmaceutickej chémie, 3. Vyd. Remedika, Bratislava, SR, 480 s.

Roche, V.F., Zito, S.V., Lemke, T.L., & Williams, D.A. (2019). Foye´s Principles of Medicinal Chemistry, 8. Vyd. Wolters Kluwer Health Adis (ESP), Baltimore, USA, 1168 s.

Silverman, R.B., & Holladay, M.W. (2015). The Organic Chemistry of Drug Design and Drug Action. 3. Vyd. Elsevier, Waltham, USA, 521 s.

Wermuth, C., Aldous, D., Raboisson, P., & Rognan, D. (2015). The Practice of Medicinal Chemistry. 4. Vyd. Academic Press (Elsevier), San Diego, CA, USA; Kidlington, Oxford, Veľká Británia, 903 s

Successful passing of the exam

Slovak language

Lecturers: prof. RNDr. Peter Mikuš, PhD, prof. Ing. Vladimír Frecer, DrSc., doc. PharmDr. Ivan Malík, PhD., doc. Mgr. Fils Andriamainty, PhD., Dr.h.c. prof. RNDr. Jozef Čižmárik, PhD., doc. PharmDr. Miroslava Sýkorová, PhD., PharmDr. Vladimír Garaj, PhD.

Pharmaceutical/Medicinal Chemistry is a science unto itself, a central science positioned to provide a molecular bridge between basic science of biology and clinical science of medicine (analogous to chemistry being the (central) science between traditional disciplines of biology and physics). From a very broad perspective, a drug design may be divided into two phases fundamental concepts about: a) drugs, receptors, and drug–receptor interactions; b) drug–receptor interactions applied to human disease. Pharmaceutical/Medicinal Chemistry is interdisciplinary, drawing very suitably on Theoretical Chemistry, Organic Chemistry, Analytical Chemistry, Molecular Biology, Pharmacology, and Biochemistry. Despite these complexities, Pharmaceutical/Medicinal Chemistry has its own clear line – the design and discovery of drug molecules with a comprehensive and precise definition and characterization of their properties, taking into account i) structural integrity of the drug molecules (in pharmaceutical, pharmacokinetic and pharmacodynamic phase, respectively), ii) their structural fragments (pharmacophore, toxicophore, metabophore, biophore, etc.; interchangeable bioisosteres), iii) structural properties, iv) physicochemical features (solubility, surface activity, acid-base and lipohydrophilic properties, stability), v) shape properties (geometric, conformational, topological, steric), vi) stereochemical properties (optical isomers, enantiomers, geometric isomers), estimation of binding affinities (in vitro ligand binding assays) and impact of the drugs - enantiomers and isomers to relevant biological targets), vii) electronic properties. Following that knowledge, structure–biological activity relationships and/or structure-pharmacokinetics relationships and/or structure-toxicity relationships are comprehensively investigated (SAR, STR, QSAR).

Expansion and intensification of knowledge from pharmaceutical chemistry the can be used by the student to formulate scientific hypotheses to create a basis for the analytical part of the dissertation and to formulate conclusions following the obtained results.

J. Krätsmár-Šmogrovič a kol.: Všeobecná a anorganická chémia., Osveta Martin (2007).

R. Chang: General Chemistry: The Essential Concepts, McGraw Hill; 7. vydanie (2013).

C. Housecroft, A. Sharpe: Inorganic Chemistry, Pearson, 5. vydanie (2018).

C. Altavilla, E. Ciliberto: Inorganic Nanoparticles. Synthesis, Applications, and Perspectives, CRC Press (2010).

Successfully passed exam

Slovak lankuage, partly English for the study of literature

Teachers: doc. Ing. Martin Pisárčik, CSc., Ing. Ladislav Habala, PhD.

Properties, electronic structure and chemical reactivity of transition metals that are a basis for the formation of inorganic nanoparticles. The basic principles of coordination chemistry and coordination chemistry of metals. Chemistry of selected p-block elements in relation to modern nanotechnology applications. Inorganic nanoparticles in pharmacy. Synthesis of metal nanoparticles and their physical properties. Experimental methods for the characterisation of nanoparticles. Stabilisation of nanoparticles. Biological activity of nanoparticles and applications.

Upon the subject completion, PhD student gains a more detailed knowledge of inorganic chemistry that is related to both inorganic chemistry basics as well as current trends with the emphasis on inorganic nanoparticles, their physico-chemical properties and potential biological activity.

1. Devínsky, F., Ďurinda, J., Lacko, I., Valentová J.: Organická chémia pre farmaceutov. Martin : Osveta, 2013. 805 s. (učebnica); 2. Favre a, Powell, H.: Nomenclature of Organic Chemistry, Royal Society of Chemistry, 2014,1068 s. , Lukáč M., Devínsky F.: Organická syntéza. Laboratórny manuál.. Bratislava, UK, 2015. 144 s.

Completion of prescribed PhD lectures and seminars; passing the exam.

Slovak language

Lecturers: doc. PharmDr. Miloš Lukáč, PhD., doc. PharmDr. Jindra Valentová, PhD.

The theoretical teaching contains basic principles of chemical bonds origin and the spatial structure of organic compounds with a reflection on their physical-chemical properties. The main attention is paid to the individual sorts of stereoisomerism, electron effects, acid-based characteristics and salt forming, to the development and significance of conjugated and aromatic systems, and, first and foremost in terms of reactivity and behaviour in biological systems.

The main attention is also paid to systematic organic chemistry. According to each group of compounds the course deals with their physical-chemical characteristics, properties, reactivity, types and mechanisms of reactions with emphasis on the importance in chemistry of pharmaceuticals and other following chemical courses of pharmaceutical study. As for natural substances only basic knowledge is provided. When teaching the subject emphasis is placed on the use of acquired knowledge of organic chemistry in pharmacy and medicine.

After completing the course, the PhD student is able to work independently in all areas of drug development and not only where knowledge of organic chemistry is required.

The course provides a comprehensive preparation of theoretical organic chemistry, as well as practical training in the field of organic synthesis focusing on the field of selected pharmaceutically important compounds. The gained knowledge and skills are necessary for the completion of the other chemical courses and are also needed for the pharmaceutically oriented courses, e.g. Pharmaceutical Chemistry, Biochemistry, Analytical Chemistry, Pharmacology, Toxicology, Pharmaceutical Technology.

Mikuš, P., Piešťanský, J., Dokupilová, S.: Kvapalinová chromatografia, hmotnostná spektrometria a ich kombinácie vo farmaceutickej a biomedicínskej analýze, VEDA, Bratislava, 2018. 365s.

Mikuš, P., Piešťanský, J.: Kapilárna elektroforéza, hmotnostná spektrometria a ich kombinácie vo farmaceutickej a biomedicínskej analýze, VEDA, 2014. 310 s.

Mikuš, P., Maráková, K.: HYPHENATED ELECTROPHORETIC TECHNIQUES IN ADVANCED ANALYSIS, Bratislava, KARTPRINT, 2012. 217 s.

Mikuš, P., Hanko, M., Piešťanský, J., Maráková, K., Dokupilová, S., Mikulová, M.: Analytical chemistry: Instrumental analysis. Bratislava : VEDA, in preparation.

Mikuš, P., Mikušová, V.: Analytical chemistry: Chemical analysis. Bratislava : VEDA, 2022.

Tekeľ, J., Mikuš , P.: Vybrané kapitoly z analytickej chémie. Analýza látok v biologických systémoch. Bratislava : UK, 2004, 192 s

Světlík, J.: Molekulová spektroskopia a optické metódy. Bratislava : UK, 2006. 81 s.

Garaj, J., Bustin, D., Hladký, Z.: Analytická chémia. Bratislava, Alfa 1989. 740 s.

Havránek, E. a kol.: Laboratórne cvičenia z analytickej chémie III. Fyzikálno-chemické metódy. Bratislava : UK, 2007. 91 s.

Křenek, P.: Analýza organických látok. Bratislava : UK, 2007. 80 s.

Vybrané kapitoly budú poskytnuté v elektronickej forme.

Successful completion of the exam.

Slovak language

Teacher: prof. RNDr. Peter Mikuš, PhD., prof. RNDr. Emil Havránek, CSc., PharmDr. Katarína Maráková, PhD., PharmDr. Juraj Piešťanský, PhD.

Analysis of organic bioactive substances, levels of drugs and their metabolites, degradation products and biomarkers of diseases in biological materials (blood, urine, tissues, etc.).

Analysis of new organic molecules (potential drugs and drug carriers for innovative dosage forms) in reaction mixtures from organic syntheses and isolated products.

Inorganic analysis of biogenic and toxic elements in individual components of the environment (air, soil, herbal drugs, water).

Bioinorganic analysis of new metal complexes in reaction mixtures from organic syntheses and isolated products.

Use of modern instrumental techniques:

• chromatographic (HPLC, GC) and electromigration separation methods (CZE, ITP, IEF, EKC) and their mutual combinations (2D HPLC, 2D / 3D CE) with integrated sample pretreatment for separation of complex (multicomponent) mixtures of substances

• spectral methods UV-VIS, FS and LIF (for rapid quantitative evaluation of substances in simple matrices), MS, MS / MS, NMR, IR, Raman spectroscopy, EPR, XRC / XRD (for detailed structural analysis molecules and their complexes)

• combined separation and spectral methods (LC-UV / MS, CE-UV / LIF / MS, etc.) to identify and determine trace levels of analytes in simple and complex (multicomponent) matrices (biological samples, dosage forms, synthetic reaction mixtures, isolated products from reaction mixtures)

• electrochemical methods with conventional and advanced sensors (biosensors) for rapid determination of selected substances in simple and complex matrices

• radioanalytical methods: radionuclide X-ray fluorescence analysis (RRFA) for direct determination of elements in solid materials

• methods of analysis of light scattering and electron microscopy for the analysis of nanostructures (shape, size/dimensions, distribution of nanoparticles)

• methods of (semi) preparative chromatography for separation and isolation of selected components from reaction mixtures

Instrumental analytical methods:

Principle of the method, experimental setup (instrumentation), methods of qualitative and quantitative evaluation, analytical and application potential. Optimization, validation and application of methods.

Electrochemical methods:

Potentiometry

Voltammetry (DPV, SWV, CV)

Ion selective electrodes

Biosensors

FIA

Separation chromatographic analytical methods:

Planar and column chromatography

High performance liquid chromatography.

Ion exchange chromatography.

Gas chromatography.

Multidimensional techniques (2D HPLC, SPE-HPLC)

Combining HPLC with advanced detection techniques (HPLC-MS, HPLC-MS / MS)

Separation analytical methods of electromigration:

Electrophoresis in planar arrangement, electromigration techniques in capillary arrangement.

Capillary zone electrophoresis (CZE).

Capillary isotachophoresis (ITP).

Isoelectric focusing (IEF).

Electrokinetic chromatography (EKC).

Capillary gel electrophoresis (CGE).

Capillary electrochromatography (CEC).

Multidimensional techniques (2D CE, 3D CE)

CE coupling with advanced detection techniques (CE-LIF, CE-MS, CE-MS / MS).

Separation preparative chromatographic and electromigration methods:

(semi) preparative liquid chromatography.

Preparative isotachophoresis.

Spectral analytical methods:

Emission spectral analysis

Fluorescence analysis

Atomic absorption spectrophotometry

Molecular absorption spectroscopy in the visible and ultraviolet region of the spectrum

Infrared spectroscopy

Raman spectroscopy.

Mass spectrometry.

Nuclear magnetic resonance.

Non-spectral optical methods:

Refractometry.

Polarimetry.

X-ray crystallographic and diffraction analysis (XRC, XRD).

Electron paramagnetic resonance (EPR).

Detectors:

Optical spectrometric detectors - absorption, fluorescence, MS, non-spectrometric

Electrochemical detectors,

Radiometric detectors

Nuclear analytical methods:

Nuclear analytical indicator methods - radiochromatography, isotope dilution analysis, radioimmunoassay and their use.

Nuclear analytical methods based on natural radioactivity.

Activation analysis.

Nuclear analytical methods - non-activation interaction analysis.

Beta-dispersion analysis.

Radionuclide X-ray fluorescence analysis.

Identification of β and γ radiation.

Other analytical methods:

Methods based on light scattering analysis.

Electron microscopy.

Statistical processing of analytical results and validation of analytical methods and procedures:

Validation parameters (precision, accuracy, linearity, sensitivity, LOD, LLOQ, LOQ, selectivity, robustness, stability, recovery, matrix effect, sample throughput, carry over).

Testing statistical hypotheses.

Validation protocols (ICH, FDA).

After completing the course, the doctoral student will gain advanced theoretical knowledge in the use of modern instrumental analytical methods chromatographic, electromigration, electrochemical, spectral (MS, NMR, IR, UV-VIS, Fluorescent) and nuclear analytical as well as multidimensional techniques (SPE-HPLC, HPLC- HPLC, CE-CE, MS / MS and combinations thereof) in pharmaceutical and biomedical analysis. An integral part of the acquired knowledge are methods of preparation of pharmaceutical and biological samples as well as environmental samples by conventional (off-line) and advanced (on-line) techniques for the mentioned analytical methods. In connection with the synthesis and structural analysis of (i) new molecules as potential drugs or drug carriers for innovative dosage forms as well as (ii) innovative materials (nanostructures) as part of analytical systems and dosage forms, the doctoral student will gain knowledge and skills also for other specific approaches and techniques such as Raman spectroscopy on-line coupled with microwave synthesis, semi-preparative chromatography, electron microscopy, and light scattering-based structural analysis techniques.

Atkins, P. W.: Fyzikálna chémia: časť 1, 2a, 2b, 3. Bratislava: STU 1999.

W.J. Moore: Fyzikální chemie, SNTL, Praha 1981

Cevc G.: Phospholipids handbook. Marcel Dekker, Inc. New York (1993)

Mouritsen O.G.: Life – as a matter of fat. The emerging science of lipodomics. Springer – Verlag Berlin Heidelberg (2005)

Kováč Š, Leško J.: Spektrálne metódy v organickej chémii, Bratislava, Alfa, 1980

Serdyuk I.N., Zaccai N.R., Zaccai J.: Methods in Molecular Biophysics. Structure, Dynamics, Function. Cambridge University Press, 2007

final exam

Slovak language

Lecturers: prof. Ing. Vladimír Frecer, DrSc., prof. RNDr. Daniela Uhríková, CSc., doc. RNDr. Jana Gallová, CSc., RNDr. Alexander Búcsi, PhD., Mgr. Mária Klacsová, PhD., Mgr. Norbert Kučerka, DrSc.

Physical chemistry builds upon the knowledge from physics and mathematics and is linked with additional chemical, biological and pharmaceutical areas. The scope of the subject:

Structure of atoms and molecules. Chemical bonds, intermolecular interactions.

Thermodynamics, phase transitions, solutions, partition equilibria, condensed systems.

Electrochemistry, solutions of electrolytes, potentiometry.

Chemical kinetics, reaction rates and orders, mechanism of chemical reactions. Catalysis, enzymatic catalysis. Kinetics of drug release from drug formulae.

Colloidal systems, dispersions, surface phenomena, membrane phenomena. Physical chemistry of biological membranes. Membrane channels. Passive and active transport. Lipids in drug delivery. Lyotropic and thermotropic polymorphism of lipids and methods for its study. Lipid-based nanoparticles in targeted drug delivery.

Experimental methods: UV-VIS, fluorescence, IR, Raman, NMR spectroscopy, diffraction, DSC calorimetry, mass spectrometry.

The course is intended to provide the necessary theoretical background for understanding of physicochemical principles in specialized areas: preparation and optimization of drugs formulae, analysis and testing of drugs, mechanism of drug action at molecular level, drug absorption, transport across biological membranes, pharmacodynamics and pharmacokinetics.

Physical background of experimental methods used for development of new drugs and mechanisms of their action is emphasized.

D. Voet, J. Voet: Biochemistry, 4th ed., John Wiley & Sons, 2010.

D. Dobrota a kol.: Lekárska biochémia, Osveta, Martin, 2016.

G. Litwack: Human Biochemistry, 1st ed., Elsevier, 2017.

Selected chapters will be provided in electronic form.

Successful completion of the exam.

Slovak language

Lecturers: doc. Mgr. Andrea Bilková, PhD.; doc. Mgr. Martina Hrčka Dubničková, PhD.; doc. PharmDr. Marek Obložinský, PhD.; RNDr. František Bilka, PhD.; Ing. Ľudmila Pašková, PhD.

 Dynamic concept of properties and functions of the biological system.

 DNA, RNA: composition, bonds and stability, biological significance.

 Biomembranes, respiratory chain, generation of energy.

 Metabolism of nutrients – interrelationship, thermodynamic aspect, energetical aspect, biological oxidations.

 Enzymology of nutrient metabolism – catabolism and anabolism – carbohydrates, simple and complex lipids, amino acids, nucleotides, proteins.

 Enzyme kinetics.

 Basic issues of xenobiochemistry and its attributes.

 Integration of metabolism in terms of physiological and pathological conditions of the organism.

 Experimantal techniques with animal and plant cell cultures.

 Plant biochemistry: nitrogen metabolism, enzymology of secondary metabolites, signalling cascades.

After completing selected chapters in biochemistry, the PhD.-student can manage (i) basic biochemical and molecular-biological analyzes, (ii) methodical procedures related to protein analysis techniques, and (iii) enzymological studies on cellular and molecular levels. The student will obtain knowledge about metabolic pathways and their regulation at the level of (i) signaling molecules, (ii) localization at a subcellular level, and (iii) monitoring of gene expression, which creates the precondition for studying the drug mechanism of individual pharmacotherapeutic groups.

• Mikuš, P., Piešťanský, J., Dokupilová, S.: Kvapalinová chromatografia, hmotnostná spektrometria a ich kombinácie vo farmaceutickej a biomedicínskej analýze, VEDA, Bratislava, 2018. 365s.

• Mikuš, P., Piešťanský, J.: Kapilárna elektroforéza, hmotnostná spektrometria a ich kombinácie vo farmaceutickej a biomedicínskej analýze, VEDA, 2014. 310 s.

• Mikuš, P., Maráková, K.: HYPHENATED ELECTROPHORETIC TECHNIQUES IN ADVANCED ANALYSIS, Bratislava, KARTPRINT, 2012. 217 s.

• Tekeľ, J., Mikuš , P.: Vybrané kapitoly z analytickej chémie. Analýza látok v biologických systémoch. Bratislava : UK, 2004, 192 s.

• Mikuš, P., Hanko, M., Piešťanský, J., Maráková, K., Dokupilová, S., Mikulová, M.: Analytical chemistry: Instrumental analysis. Bratislava : VEDA, pripravuje sa.

• Havránek, E. a kol.: Laboratórne cvičenia z analytickej chémie III. Fyzikálno-chemické metódy. Bratislava : UK, 2007. 91 s.

• Světlík, J.: Molekulová spektroskopia a optické metódy. Bratislava : UK, 2006. 81 s.

• Labuda, J. a kol, Analytická chémia, Bratislava, STU v Bratislave, 2019, 682 s.

• Magulová, L.: Metodický list racionálnej farmakoterapie 15./16., Terapeutické monitorovanie hladín liečiv, Ročník 5, Číslo 1-2, 2001. (plus citovaná literatúra)

• Vedecké publikácie registrované v databáze Web of Science: kľúčové slová: Mikus (author), Comenius (Address), amino acids, biogenic amines, thiopurines (Topic)

Successful completion of the exam.

Slovak language, English language

Teacher: prof. RNDr. Peter Mikuš, PhD., PharmDr. Juraj Piešťanský, PhD.

The basic concepts/terms, principles, methodological and clinical aspects, validation and application areas of the master's curriculum are continuously supplemented with current knowledge/findings and solutions to the problems of analytical monitoring of drug levels in practice.

 Introduction to the issue

 Clarification of the term “therapeutic drug monitoring”

 Importance of TDM in clinical practice (current state of the issue)

 Analytical aspects in TDM

 Pharmacological aspects in TDM

 Monitoring the levels of biologically active substances for toxicological, doping and forensic analysis

 Groups of therapeutically monitored drugs

 Drugs with a narrow therapeutic range

 Drugs with a well-defined relationship between drug concentration and effect (therapeutic or toxic)

 Drugs with large inter- or intra-individual differences in drug distribution or clearance

 Distribution of drug groups (by effect)

 Antibiotics with nephrotoxic and ototoxic effects (aminoglycosides amikacin, gentamicin, netilmicin, tobramycin, polypeptide antibiotic vancomycin)

 Cardiovascular drugs (cardioglycosides: digoxin, antidysrhythmics: quinidine)

 Antiepileptics (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, valproic acid)

 Tricyclic antidepressants (amitriptyline, imipramine, clomipramine)

 Antiasthmatics (theophylline)

 Immunosuppressants (cyclosporin A, tacrolimus, azathioprine, 6-mercaptopurine, 6-thioguanine)

 Cytostatics (methotrexate)

 Groups of other monitored substances

 Diagnostic biomarkers - endogenous substances

 Low molecular weight organic substances (amino acids, carboxylic acids, biogenic amines, lipids, etc.)

 Inorganic ions (metal cations, anions)

 Biomolecules (proteins, e.g., enzymes, antibodies)

 Toxic and prohibited substances (doping, drugs, poisoning) and drugs applied without the consent of a doctor (self-treatment) - exogenous substances

 Commercial drugs (clenbuterol, ivermectin, etc.)

 Experimental drugs (SARMS, etc.)

 Illegal synthetic preparations (heroin, etc.)

 Natural toxins (amanitin, botulinum toxin, etc.)

 Collection and processing of biological material

 Sampling (method, time intervals), steady state, number of samples, residual and peak concentration vs. toxicity and therapeutic effect

 Sample processing (sample type, sample preparation before analysis, sample preparation techniques / methods - protein precipitation, extraction, derivatization, protein cleavage, etc.)

 Sample storage

 Methods of biological material analysis

 Development (optimization), validation and application of analytical methods, advantages and limitations of analytical methods

 Spectral methods

 Electrochemical methods

 Separation methods (chromatographic, electromigration)

 Hyphenated separation and spectral or electrochemical methods

 Separation methods with on-line sample preparation

 Immunochemical methods: radioimmunoassay (RIA), immunoenzyme methods (EIA, EMIT, ELISA, FPIA, MEIA, CMIA)

 Interpretation of analytical results

 TDM: Interpretation of serum drug concentrations in the context of all clinical data (related areas: pharmacokinetics and pharmacodynamics of drugs)

 Diagnosis of diseases: correlations of levels of individual biomarkers or biomarker profiles in comparison groups (monitoring of changes in datasets of health vs patients)

 Toxicological, anti-doping, forensic analysis: monitoring of levels of monitored substances, limit concentrations

 Statistical evaluation of the analytical results

 Validation parameters according to the used validation protocol

 Validation protocols: FDA, ICH

 Hypothesis testing (Student's t-test, ANOVA)

 Use of therapeutic drug level monitoring data:

 Objective: to ensure maximum efficacy of drugs, to reduce the risk of drug toxicity, to maintain the concentration of drugs in the so-called "Therapeutic range"

 Monitoring of treatment of chronically and critically ill patients with altered drug clearance with a narrow therapeutic range, patients with different drug pharmacokinetics (elderly, children)

 Adjust batch modes (regimes)

 Optimization of therapy using pharmacokinetic programs (population-kinetic data)

 Determining patients' compliance with treatment

 Identification of drug toxicity risks (reduction of toxic drug reactions)

 Reduction of treatment costs

 Reducing the need for emergency procedures and hospitalizations

 Shortening the length of hospitalization

 Application areas - solved examples:

 TDM of thiopurines in the optimization of therapy of patients with non-specific inflammatory bowel diseases

 Monitoring of carboxylate levels in connection with the diagnosis and therapy of cancer patients

 Monitoring of Prohibited Substance Levels (Clenbuterol, SARMS) in connection with doping control

Reliable identification and quantification of drugs in biological systems are essential steps to understand the mechanisms of their action in a living organism. Drug concentration levels are an important indicator of the therapeutic process at the molecular level, usable in optimizing the treatment management of individual patients.

Therapeutic drug monitoring (TDM) is recommended and performed for (i) drugs with a narrow therapeutic range, (ii) drugs with a well-defined relationship between drug concentration and effect (therapeutic or toxic), (iii) drugs with large inter- or intra-individual differences in drug distribution or clearance. Integral components of TDM are (I) collection and processing of biological material, (II) development, validation and application of analytical methods, and (III) processing and interpretation of analysis results. Interpretation of TDM results requires adequate knowledge of the pharmacokinetics and pharmacodynamics of the monitored drugs and their association with the patient's clinical data. Thus, for the successful implementation of TDM in clinical practice, it is necessary to combine theoretical knowledge and practical aspects of methods of clinical analysis and clinical pharmacology. In a broader context, monitoring of biologically active substance levels is also carried out in the areas of disease diagnosis, toxicology, doping control, forensic analysis and other practical areas. The graduate of the course will gain knowledge related to the development and application of analytical methods and procedures usable in solving the tasks of the above areas of pharmaceutical practice.

The doctoral students will expand and deepen their knowledge of the latest findings in the field of analytical monitoring of drug levels in practice in connection with the relevant analytical methodology and clinical aspects of the analyzed substances. They will be able to apply the acquired knowledge in practice at various levels of activity in connection with optimization of therapeutic procedures, early diagnosis of diseases, assessment of patient compliance, assessment of intoxication or presence / levels of banned, narcotic and psychotropic substances in the biological system in cooperation with physicians, clinical, diagnostic, toxicological, anti-doping or forensic laboratories.

Brunton LL, Hilal-Dandan R, Knollmann BC et al. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e, McGraw-Hill Education 2018

Golan D. E., Tashjian Jr A. H.., Armstrong E. J., Armstrong A. Wet al. .: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3rd 4th Edition. Lippincott Williams&Wilkins, 20172

Katzung BG, Vanderah TW et al. : Basic & Clinical Pharmacology, 15e, McGraw Hill 2021

Rang, H.P., Dale, M.M. a kol.: Rang and Dale´s Pharmacology, 7th ed. London, Churchill Livingstone, Elsevier, 2012

Ritter JM. et al.: Rang and Dale's Pharmacology E-Book, Elsevier, 9th ed., 2018

Successful passing of the exam

Slovak language, English language

Lecturers: prof. PharmDr. Adriana Ďuriš Adameová, PhD.; prof. PharmDr. Ján Klimas, PhD., MPH.; doc. Peter Křenek, PhD.; doc. PharmDr. Anna Paul Hrabovská, PhD.; doc. PharmDr. Marek Máťuš, PhD.; Mgr. Peter Vavrinec, PhD.; Mgr. Diana Vavrincová, PhD

The focus is on one or more of the following areas of pharmacology:

- pharmacodynamics with respect to the mechanism of action of drugs

- pharmacokinetics

- pharmacogenomics

- adverse effects of drugs

- drug overdose

- therapeutic use of drugs

Special pharmacology

- pharmacology of drugs with effect on the central nervous system

- pharmacology of drugs with effect on the autonomous nervous system

- pharmacology of drugs with effect on the smooth muscles

- pharmacology of drugs with effect on the cardiovascular system and kidneys

- pharmacology of blood, inflammation

- pharmacology of drugs with effect on the respiratory system

- pharmacology of drugs with effect on the gastrointestinal system

- pharmacology of drugs with effect on the endocrine system

- pharmacology of anti-infective drugs

- pharmacology of anticancer drugs

- new directions of therapy of diseases using biological drugs

Expansion and intensification of knowledge from pharmacology the can be used by the student to formulate scientific hypotheses to create a basis for the analytical part of the dissertation and to formulate conclusions following the obtained results.

Chalabala, M. a kol.: Technologie léků. 3. vyd. Praha: Galén, 2006. 399 s. Žabka, M. a kol: Moderné lieky vo farmaceutickej technológii. Bratislava: SAP, 1999. s.487 European Pharmacopoeia 10 th Ed. Strasbourg: EDQM, 2022 Aulton, M. E.: Aulton´s Pharmaceutics: the design and manufacture of medicines - Edinburgh: Churchill Livingstone, 2018 Mikušová, V.; Mikuš, P.: Advances in Chitosan-Based Nanoparticles for Drug Delivery. Int. J. Mol. Sci. 2021, 22, 9652. https://doi.org/10.3390/ijms22179652

Successful passing of the exam

Slovak language, English language

Lecturers: PharmDr. Veronika Mikušová, PhD., PharmDr. Juraj Piešťanský, PhD., doc. RNDr. Miroslava Šupolíková, PhD.

Pharmaceutical preparations are of a dosage (application) form which depends on the means of administration and coexistence of relevant drugs and excipients. Pharmaceutical technology (galenics) deals with composition, formulation, production, evaluation, and quality assurance of individually prepared and manufactured pharmaceutical preparations. It studies conditions for formulation of drugs and excipients into pharm. preparations, rules governing these processes, relations of the preparation with the effect of contained drugs. The subject of the study are these areas: - Pharm. preparations as systems composed of drugs and excipients (constitutive, stabilizing, corrective, etc.), conditions for coexistence of components in pharm. preparation. - Procedures and devices for preparation and manufacturing of pharm. preparations - Evaluation and quality assurance of pharm. preparations in terms of composition, technology, structure - Relations between the pharm. preparation and bioavailability of administered drugs - Stability of pharm. preparations and its possible ensuring - Containers ‘materials, technique for pharm. preparations ‘containers, study of interactions between containers and drugs / excipients Current research is oriented to drug carriers (polymeric, lipid - liposomes) in the role of drug delivery systems as nanoparticles. It begins with the synthesis of the carrier, incorporation of the drug, continues with formulation of dosage form, stability studies of formulated particles and in vitro drug release study. At the end of this difficult process the biologic activity and in vivo bioavailability are evaluated in cooperation with other departments/institutions. Also, nanodispersion systems as e.g., micro- and nanoemulsions are studied, especially related to low soluble drugs (e.g., terbinafine, minoxidil, indomethacin, tretinoin) intended for topical application with local or systemic effect e.g., also using the mechanisms of transdermal passage. In the preparation of these systems, various types of polymers (e.g., chitosan, thermosensitive polymers) and specific excipients are used to create a specific structure of given formulation with improved properties (e.g., better bioadhesion, stability, capacity to release the low soluble drugs, improved permeation, and penetration to target tissues in required concentration).

By passing the course, the PhD. student will have a complex theoretical knowledge of drugs as dispersion and application systems in terms of theoretical and practical preparation of innovative dosage forms.