The Laboratory of Analytical Chemistry and Pharmacology focuses on the qualitative and quantitative analysis of low molecular weight bioactive substances in various biological samples using LC-MS/MS. Most of the analyses aims at determining pharmacokinetic properties (absorption, distribution, metabolism, elimination and time variations in concentration) of drugs used in therapy and drug candidates in preclinical development. Within the analyses, mainly samples of body fluids (blood, plasma, serum, etc.) or soft tissues are processed. The first step is usually homogenization of biological samples, then adjustment by a selection agent (e.g. deproteinization) and concentration by different techniques of direct extraction, LLE or SPE. In LC applications, conventional methods with reverse phase, ion-pairing or hydrophilic interaction chromatography are routinely employed. Detection with a hybrid quadrupole-orbitrap high resolution mass spectrometer also enables to examine the stability and possible degradation products of the analytes. In such cases processing of complex data from tandem mass spectrometric analyses (MS/MS) is performed using special software. Further analytic implementations used in the laboratory include searching for relationships between the structure and retention properties, modeling of passive diffusion across the cell membrane, accurate molecular weight measurements and identification of products from various stages of advanced organic syntheses. The development of bioanalytical methods and their validation is carried out according to the recommended GLP principles.
Pharmacokinetic analysis is an essential part of drug development which tries to monitor the fate of drugs in the body. Thanks to rational methods of drug design it is indeed possible to predict some important pharmacokinetic properties, but experimental results of pharmacokinetic studies cannot currently be replaced in drug development. Promising chemical compounds that have demonstrated a high pharmacodynamic efficiency and low cytotoxicity in vitro, are submitted to preclinical testing in animals (mouse, rat, guinea pig, rabbit, pig). In the experimental studies on animals bioethical guidelines and applicable laws of the Czech Republic and the EU, which protect the rights of animals and reject their unnecessary suffering, are respected. Satisfactory results from preclinical animal studies are a prerequisite for admission of drug candidates to human clinical trials.
The object of the analytical and pharmacological studies in this laboratory is evaluation of chemical substances which may be used for instance as drugs against Alzheimer's disease, cancer, Myasthenia Gravis or as antidotes in organophosphate poisoning. In the above mentioned analytical laboratory activities we can offer cooperation.
