Victoriya Georgiyants

Pharmaceutical companies in Ukraine aspire to develop their innovative medicinal products and successfully introduce them to the global market. However, along with the prospects of increased usage of these pharmaceuticals, there arises a challenge of heightened waste production, making them a part of the over twenty million tons of PPCPs produced annually. Consequently, one of the tasks in producing new pharmaceuticals is the development of methodologies and approaches not only for quality control but also for their determination in the environment matrices.
 The aim. Develop and validate GC-FID chromatographic method for the simultaneous determination of Enisamium iodide and Tilorone dihydrochloride, evaluate their applicability, and compare their "greenness" with the previously developed HPLC method.
 Materials and methods. The determination of the Tilorone dihydrochloride and Enisamium iodide was carried out by gas chromatography with a flame ionization detector using the Rxi-5 ms (30 m long, 0.25 mm outer diameter and 0.25 μm liquid stationary phase thickness)
 Results. Chromatographic GC-FID methods have been developed for the simultaneous determination of Enisamium iodide and Tilorone dihydrochloride. Optimal sample preparation conditions were established, and a validation process was conducted. A comparison with the previously developed HPLC method was made regarding "greenness."
 Conclusions. The developed GC-FID methodology is accurate and more environmentally friendly compared to the previously established methods. It can be recommended to determine Enisamium iodide and Tilorone dihydrochloride in the environmental matrices. It is considered environmentally friendly based on the overall GREENness (AGREE) scale, scoring 0.73 (>0.70), which demonstrates the environmentally favourable nature of the proposed analytical approach

Aim. Given the incompleteness of literature data on the solubility of quercetin and the importance of this physicochemical characteristic in the study of its bioavailability, there is a need to develop an alternative method for accurately quantifying the solubility limit of quercetin.
 Materials and methods. The concentration of quercetin in the samples was determined by directly determining the total organic carbon. For measurements, a total organic carbon analyzer 450 TOC (METTLER TOLEDO) was used with a range of measured values of 0.05–1000 ppbC µgC/l.
 Results. The exact limit of the solubility of quercetin, as a poorly soluble substance, has been established. Having previously measured the value of total organic carbon in the prepared solutions, we obtained data on the concentration of quercetin in solutions depending on the pH of the solution.
 Having built a graphical dependence of the measured values of the concentration of a substance on the pH values of the studied solutions, we obtain a mathematical equation of the reliance. Using the resulting function equation, one can approximate the concentration value of a substance with a pH value of 7.0. This value will be the solubility limit of the test substance for neutral media.
 Conclusions. As a result of the research, a new method was proposed for the quantitative determination of the solubility limit of a substance, with an accuracy not exceeding 5.0 %. The method is based on measuring the concentration of total carbon in acidic solutions with different pH values and subsequent approximation of the obtained dependence of the pH value equal to 7.0

Introduction: An analysis of the literature on the painkillers long used in traditional medicine, which are isolated from plant materials, has shown that many of them are alkylamides of various carboxylic acids. This fact served as the basis for the study of a large group of N-alkyl-4- methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as potential new analgesics. The objects of the study were synthesized in the traditional way involving the initial conversion of 4-methyl- 2,2-dioxo-1H-2λ6,1- benzothiazine-3-carboxylic acid to imidazolide, in which imidazolide was used as an acylating agent. The method is simple to implement and, as a rule, gives high yields of final alkylamides. However, in reaction with sterically hindered tert-butylamine, along with the “normal” product, an unexpected formation of N-tert-butyl-4-methyl-1-(4-methyl-2,2-dioxo-1H-2λ6,1- benzothiazine-3-carbonyl)-2,2-dioxo-2λ6,1-benzothiazine-3-carboxamide was observed, which was characterized by X-ray diffraction analysis as a monosolvate with N,N-dimethylformamide. These synthetic problems can be avoided using a more powerful acylating agent, 4-methyl-2,2-dioxo-1H- 2λ6,1- benzothiazine-3-carbonyl chloride. Background: A large group of new N-alkyl-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3- carboxamides was synthesized. Objective: On the basis of molecular docking, some derivatives of N-alkyl-4-methyl-2,2-dioxo-1H- 2λ6,1-benzothiazine-3-carboxamides have been designed. Their preliminary structure-activity relationships (SAR) have been studied. The most rational approaches to the synthesis of lead compounds have been developed. The most active compounds have shown high anti-inflammatory and analgesic activities. Methods: The structure of all compounds prepared has been confirmed by the data of elemental analysis, 1H- and 13C NMR spectroscopy, and electrospray ionization liquid chromato-mass spectrometry. For rational drug design, optimization of further pharmacological screening and prediction of a possible mechanism of pharmacological action, molecular docking has been performed. For the determination of activity, pharmacological studies have been carried out. Results: Pharmacological tests have determined that the transition from N-aryl(heteroaryl) alkylamides to “pure” N-alkylamides we carried out is accompanied by a significant reduction and even complete loss of anti-inflammatory effect with remaining analgesic activity. Conclusion: According to the studies, compounds from N-alkyl-4-methyl-2,2-dioxo-1H-2λ6,1- benzothiazine-3-carboxamides are potential anti-inflammatory and analgesic agents.