Quetiapine fumarate (an antipsychotic) is part of numerous generic drugs that are in fairly wide demand among the population, therefore, more and more data appear on the counterfeiting and smuggling of funds, as well as non-medical use, which are life-threatening for the population and explain the high prevalence of the active ingredient as object of forensic examination. The aim. To develop an algorithm for conducting a forensic pharmaceutical examination and propose a method for determining quetiapine fumarate for forensic pharmaceutical purposes. Materials and methods. All studies were performed using reagents that meet the EP, USP and USPU requirements, Class A glassware and qualified devices. Identification by IR spectroscopy was performed in the range from 500 to 4000 cm-1 on the device “Nicolet 380 FT-IR Spectrometer by Thermo Fisher Scientific” using a prefix “Smart Perfomer” with a ZnSe crystal. The UV absorption spectra of the solutions were recorded using a Specord 205 spectrophotometer from Analytik Jena AG (Germany). TLC was performed on Merck chromatographic plates (silica gel 60G F254, Germany). The following systems were used as mobile phases: hexane – acetone – 25 % ammonia solution (60: 40: 2); methanol – 25 % ammonia solution (100: 1.5), hexane – acetone – 25 % ammonia solution (50: 45: 5). Detection was performed under UV light (254 nm), followed by spraying with Dragendorff reagent. Analysis by gas chromatography with mass detection was performed using a GC gas chromatograph with a mass spectrometric detector GCMS-QP2020. Data were analyzed using the program: GCMSsolution, LabSolutions Insight (Shimadzu Corporation, Tokyo, Japan). Results. An algorithm for conducting a forensic pharmaceutical examination in accordance with the current legislation of Ukraine has been developed, methods for determining quetiapine for forensic pharmaceutical purposes have been proposed. Conclusions. The developed methods for determining quetiapine meet the requirements of the current legislation of Ukraine and the Ministry of Justice of Ukraine. The obtained data prove the high sensitivity and reproducibility of the methods and prove the possibility of their introduction into the practice of forensic examination

The aim. The aim of the study was to reveal QSAR and ascertain the possible mechanism of action via docking study in the row of tricyclic quinoline derivatives with diuretic activity. Materials and methods. Pyrrolo- and pyridoquinolinecarboxamides with proven diuretic activity were involved in the study. Molecular descriptors were calculated using HyperChem and GRAGON software, and QSAR models were built using BuildQSAR software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used. Results. Multivariate linear QSAR models were built on two datasets of quinolinecarboxamides: Vol = a∙X1 + b∙X2 + c∙X3 + d, where Vol – volume of the daily produced urine in rats, Xi – molecular descriptor. QSAR analysis showed that the diuretic activity is determined by the geometric and spatial structure of molecules, logP, the energy values, RDF- and 3D-MoRSE-descriptors. Based upon internal and external validation of the models, the most informative two-parameter linear QSAR model 3а was proposed. Docking data showed the high affinity of two lead compounds to the carbonic anhydrase II. Conclusions. QSAR analysis of tricyclic quinoline derivatives revealed that the diuretic activity increases with the increase of value of logP, refractivity, and dipole moment and with the decrease of volume, surface area, and polarization of the molecules. Increase of values of such energy descriptors as bonds energy, core-core interaction, and energy of the highest occupied molecular orbital results in higher diuresis; decrease in hydration energy leads to higher diuretic activity. Based upon molecular docking calculation, the mechanism of diuretic action is proposed to be carbonic anhydrase inhibition. QSAR models and docking data are useful for in-depth study of diuretic activity of tricyclic quinolines and could be a theoretical basis for de novo-design of new diuretics