Development and validation of a novel stability indicating HPLC method for the separation and determination of darolutamide and its impurities in pharmaceutical formulations

This study reports for the first time about a stability indicating RP-HPLC method for analysis of darolutamide and its impurities 1, 2, and 3 in bulk and formulations. The separation was achieved on Phenomenex column with Luna C18 (250 mm × 4.6 mm, 5 μm) as stationary phase, and 50 mM ammonium acetate: methanol solution 15:80 (v/v) at pH 5.2 as mobile phase at 1.0 mL/min flow rate. UV detection was carried at wavelength of 239 nm. In these conditions the retention time of darolutamide and its impurities 1, 2, and 3 was 7.05, 8.90, 4.63 and 5.95 min, respectively. The method was validated for system suitability, range of analysis, precision, specificity, stability, and robustness. Forced degradation study was done through exposure of the analyte to five different stress conditions and the % degradation was small in all degradation condition. The proposed method can separate and estimate the drug and its impurities in pharmaceutical formulations. Hence, the developed method was suitable for the quantification of darolutamide and can separate and analyse impurities 1, 2, and 3

Synthesis of a hydrophilic derivative of ecdysterone and development of its water-soluble form

The article presents materials on the isolation of ecdysterone substance from medicinal plant raw materials Silene wolgensis (Hornem.) Bess. ex. Spreng (Volga smolyovka). For the first time, the optimization of the method for ecdysterone substance obtaining from the aboveground part of the superconcentrator of phytoecdysteroids of the Silene wolgensis was carried out and based on it a pilot industrial regulation for the isolation of ecdysterone and an encapsulated water-soluble form were developed. It was found, that the interaction of the substrate molecule and the clathrate forms a substance that can dissolve in water and other more polar solvents, thereby solving the problem of bioavailability of the main hydrophobic drug. The method developed for producing the substance ecdysterone and its water-soluble encapsulated with β-cyclodextrin form was implemented into production at the Karaganda pharmaceutical plant. NMR studies of changes in the chemical shifts of protons of substrates and receptors illustrated that ecdysterone interacts with β-cyclodextrin to form supramolecular inclusion complexes with stoichiometric composition of 1:1

Study of uric acid oxidation reaction products in medium of ammonia or primary amines

This work is considered in more detail the most important stage of obtaining one of the promising heteroatomic polycyclic compounds 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane (THAP). THAP is a potential compound for creating high-energy substances due to the presence of six nitrogen atoms in the structure and tight packing. Uric acid is the starting compound in the THAP synthesis chain. When it is oxidized by sodium persulfate or potassium ferrocyanide, 1,5-diaminoglycoluril is formed, from which the propellane structure is formed by the tricyclization reaction. This work expanded the range of oxidants for the conversion of uric acid to 1,5-diaminoglycoluril. It was found that 1,5-diaminoglycoluril was formed with a yield of 29 % when using equimolar proportions of uric acid and KMnO4. When using MnO2 in a ten times more excess, the yield of 1,5-diaminoglycoluril was 38 %. The article also presents the results of a study of the interaction of uric acid with some amines. The reaction of interaction of uric acid with benzylamine was studied in more detail, the reaction products of which were 4-benzylimino-5-benzylaminoallantoin, 4- benzylimino-1-benzylamino-allantoin and 4-benzyliminoallantoin. Based on the synthesis of 4- benzyliminoallantoin, a number of promising derivatives of 4-iminoallantoin were obtained, namely 4- ethyliminoallantoin, 4-propyliminoallantoin, 4-i-propyliminoallantoin, 4-n-butyliminoallantoin, 4-i- butyliminoallantoin, 4-tert-butyliminoallantoin.

A.S. Masalimov as the founder and leader of a new direction in ESR spectroscopy and quantum chemistry of free radicals

The article highlights the creative path of A.S. Masalimov, an outstanding Kazakhstan chemist who celebrates his 70th anniversary in 2022. The main stages of his career and significant events of his scientific career are presented here. The contribution of professor A.S. Masalimov in the foundation and development of the school of ESR spectroscopy and quantum chemistry at the Karaganda Buketov University is shown.

Acid dissolution of neodymium magnet Nd-Fe-B in different conditions

The separation of rare-earth elements (REE) from a neodymium magnet has been widely studied last year. During the research it was identified that the waste of computer hard disk contains 25.41 % neodymium, 64.09 % iron, and <<1 % boron. To further isolate rare-earth metals, the magnet was acidically dissolved in open and closed systems. In both methods of dissolution, concentrated nitric acid was used. The difference between these methods is the conditions of dissolution of magnet. The magnet was dissolved in a microwave sample preparation system at different temperatures and pressures in a closed system. In the open system, the acid dissolution of the magnet is conducted at room temperature. 0.2 g of the neodymium magnet sample was taken under two conditions, and the dissolution process in the closed system lasted 1 hour, and in the open system 30-40 minutes. The open system is a non-laborious, simple, and cheap method of dissolving the magnet by comparing both systems. Therefore, an open sample preparation system is used for further work. To remove the iron in the magnet, oxalic acid was used and REEs are precipitated as oxalates under both conditions. According to the result of the Inductively coupled plasma mass spectrometry (ICP-MS) method, it was identified that the neodymium and iron contents in the precipitate are 24.66 % and 0.06 %, respectively. This shows that the iron has almost completely passed to the filtrate

Recovery of used acetic acid via sulfuric acid

Kazakhstan has a huge phosphate raw material base, where the basis is made up of micro-grained phosphate ores of the Karatau basin. The depletion of reserves of high-quality commercial ores leads to the search for new methods of using the enrichment and sorting of low-grade technogenic ores, one of which is phosphate-siliceous slates. The presented study was carried out in two stages: at the first stage, phosphate-siliceous shales were enriched by the acetic acid method, regime technological parameters, kinetic and thermodynamic regularities of the process were determined. At the second stage of the research a method for recycling used acetic acid during the enrichment of low-grade phosphate-siliceous slates is proposed. In this case, sulfuric acid was chosen as the regenerating agent of acetic acid. The reliability of the performed studies was proved by the use of modern complex research methods: scanning electron microscopy, Energy Dispersive X-Ray and X-Ray difraction analyses. To determine the course of a particular reaction, a thermodynamic analysis was performed using modern HSC 6.0 software. The kinetic data are determined by calculation. The obtained experimental data were subjected to statistical analysis (Chaddock scale, standard deviation, coefficient of determination). The mechanism of interaction of an acetate solution with sulfuric acid is illustratively described. In conclusion, the sulfuric acid method is suitable for the regeneration of applied acetic acid. In this case, a by-product is formed in the form of calcium sulfate. This product can be used as a building binder (confirmed by the protocol of the “National Center of Expertise” of the Republic of Kazakhstan).

Synthesis and characterization of a new magnetic composite MnFe2O4/clay based on a natural clay obtained from Turkestan deposit

The work is devoted to the development of a new method for the synthesis of magnetic composites based on manganese ferrite on a natural clay, coupling with their physico-chemical characterization. In the study, a natural clay of Kazakhstan obtained from the Turkestan deposit was used for the preparation of magnetic composites. The formation of materials with magnetic properties is an urgent task of our time, due to the needs of various applications of magnetically controlled materials for biomedical systems, electronic devices, catalytic and adsorption processes. The advantage of such materials is the ability to control them using a magnetic field for shaking, recovery, induction heating, among others. In this work, samples were prepared by co-precipitation of manganese and iron salts with 5 mol L-1 NaOH over the Turkestan clay (TC). Materials were characterized by various analyses, such as Fourier-Transform infrared spectroscopy (FTIR), X-ray diffractometric analysis (XRD), and elemental analysis. According to the results of physical and chemical studies of the XRD and thermal analysis, kaolinite is the main mineral in the composition of TC. Magnetic adsorbents MnFe2O4/clay with perfect magnetic separation characteristics were successfully obtained by chemical co-precipitation

Synthesis and characterization of novel thermo- and salt-sensitive amphoteric terpolymers based on acrylamide derivatives

A novel linear amphoteric terpolymers based on neutral monomer — N-isopropylacrylamide (NIPAM), ani- onic monomer — 2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (AMPS), and cationic mono- mer — (3-acrylamidopropyl) trimethylammonium chloride (APTAC) were synthesized by free-radical polymerization in aqueous solution and characterized by methods of 1H NMR and FTIR spectroscopy, TGA, GPC, Dynamic light scattering (DLS) and zeta-potential. The thermal and salt sensitivity of amphoteric ternary polymers of various compositions, particularly, [NIPAM]:[AMPS]:[APTAC] = 90:2.5:7.5; 90:5:5; 90:7.5:2.5 mol.% were studied in aqueous and aqueous-salt solutions in the temperature range from 25 to 60 C and at the NaCl ionic strength  interval from 10–3 to 1M. It was found that due to hydrophobic/hydrophilic balance, the temperature dependent conformational and phase change of macromolecular chains becomes sensitive to salt addition and allows the fine-tuning of the phase transition. In aqueous and aqueous-salt solutions, the average hydrodynamic size of amphoteric terpolymers is varied from 8 to 300 nm exhibiting bimodal distribution at room temperature. The number average (Mn) and weight average (Mw) molecular weights, polydispersity index (PDI), and zeta-potentials of amphoteric terpolymers in aqueous solu- tions were determined

Invariants of ratio of crystal-mobile, liquid-mobile, and vaporized chaotized particles in solid, liquid, and gas states of substance

The authors of the article have developed the concept of chaotic particles based on the Boltzmann distribution over the kinetic energy of the particles’ chaotic motion. This distribution allows to combine the solid, liquid, and gaseous states of matter with the help of energetic particles called crystal-mobile, liquid-mobile, and vapor-mobile. The ratio of the proportions of such randomized particles determines a certain state of matter aggregation. The sum of the shares of these particles in all combinations at any temperature is equal to unity. During the study it has identified that qualitative and quantitative analysis of states with a priority basic effect of a randomized component of a substance can be conducted. Certain regularities of states were discovered, independent of the specific type of substance and consistent with the physicochemical properties. The entropy of mixing of all three energy classes of chaotic particles was calculated for simple substances. It was characterized by a maximum in the interval of the boiling point of substances. This feature testifies to the unique variety of possibilities for the implementation of the most complex heterogeneous processes in terrestrial conditions at atmospheric pressure, which ultimately ensured the self-organization of life

Synthesis, quantum-chemical calculations and virtual screening of the alkaloid cytisine derivatives

The synthesis of some cytisine derivatives was carried out in the work. The article provides the data of quantum-chemical calculation and virtual screening of the alkaloid cytisine derivatives synthesized. At the same time, the reaction centers of the cytisine derivatives molecules were determined. In order to study the reactivity of the derivatives obtained (namely cinnamoylcytisine, lipoylcytisine, and cytisinylisoalantholactone) the quantum-chemical calculations were conducted to determine the energy and charge characteristics of the molecules. The results indicate a sufficient thermodynamic stability of the cinnamoylcytisine and lipoylcytisine molecules. The cytisinylisoalantholactone molecule is not stable according to the results of quantum chemical calculations. The data on the energy values of the frontier molecular orbitals show that, in general, all molecules exhibit electrophilic properties. A bioprediction was implemented using PASS (Prediction of Activity Spectra for Substances) as one of the most efficient and well-known computer program with the aim of detailed study and the probable establishment of the biological activity of the synthesized cytisine derivatives. Based on the results of virtual screening, promising types of alkaloid cytisine derivatives were identified, which are potential sources of original drugs