Quality control of herbal medicinal products (HMPs) is challenging due to their multicomponent composition. For most HMPs, chemical reference standards (CRSs) required for traditional chromatographic and spectral analyses are unavailable. According to USP and Ph. Eur., an exception is valerian tincture, for which highly specific CRSs have been developed. The aim of this study was to use principal component analysis (PCA) and the novel two-dimensional diffuse laser scattering (2D-DLS) method to identify HMPs and their aqueous-ethanolic extracts according to their botanical genera without relying on specific marker compounds. Spectral data were compiled into an extensive library covering a wide wavelength range—from 0.02 nm to 15,000 nm. PCA of the spectral data (UV spectrophotometry, fluorimetry, FTIR spectroscopy, and X-ray diffraction) enabled clustering of samples by individual botanical genera. The most significant information for sample differentiation was provided by wavenumbers of 1400, 1180, and 931 cm−1 in the IR spectra and wavelengths of 450 nm and 672 nm in the UV and fluorescence spectra, respectively. During model cross-validation, all “blind samples” were correctly classified by botanical genus, achieving a non-error rate (NER) of 100%. Furthermore, the unique 2D-DLS method was used to rapidly identify tinctures without opening the glass bottles.

Objectives: Zinc deficiency is recognized as a significant global contributor to morbidity and mortality risk. In the absence of a reliable biological marker for determining the absorption coefficient of dietary zinc, a mathematical model is employed. This systematic review aimed to study this mathematical model and evaluate its potential to calculate the recommended dietary intake of zinc (RDI), compared to actual zinc balance in the human body. Methods: This review analyzes scientific publications from 1980 to 2025 that focus on zinc balance in the bodies of healthy individuals aged 19 and older of both sexes. Special attention is given to experimental results that demonstrate the disruption of the balance between the RDI and the quantity of zinc excreted through the intestines. Results: A systematic review of the literature has shown that the recommended dietary allowances for zinc intake, the absorption rate into the bloodstream, and the intestinal excretion of zinc—all critical factors for assessing zinc balance — exhibit substantial variations according to data from different research groups. The mathematical model used to determine the absorption coefficient and calculate dietary zinc intake norms has limitations, as it does not account for the polydentate nature of phytate ions. Conclusions: The RDI of zinc is lower than the actual requirement and needs adjustments to increase it. The analysis of the zinc balance while considering the polydentate nature of phytic acid can help to make more accurate dietary selections and recommendations for zinc-based supplements, thereby maintaining homeostasis and preventing toxic levels in the body. Keywords: zinc absorption and excretion, zinc homeostasis, phytic acid polydentency

Chemical incompatibility between active pharmaceutical ingredients (APIs) and mineral supplements may affect their bioavailability and effectiveness. Water, as the main component of physiological fluids, plays a crucial role in these interactions. Natural waters vary in the deuterium. Estimation of the kinetic isotope effect (KIE) provides valuable information on reaction mechanisms in solvents with different D/H ratios and with the replacement of protium with deuterium in API molecules. Studies of the kinetics of interactions between zinc ions and amoxicillin in water with a natural isotopic composition (D/H = 145 ppm) and in heavy water (99.9% D2O) offer a model for predicting similar interactions in vivo. The presence of chiral centers in the amoxicillin molecule allowed the use of polarimetry to study the influence of the solvent isotopic composition, temperature, and pH on the rate of interaction. In heavy water, a twofold decrease in the rate of amoxicillin binding to hydrated zinc ions was observed compared to natural water at 20 °C. Arrhenius kinetics confirmed the observed KIE: Ea = 112.5 ± 1.3 kJ/mol for D2O and 96.0 ± 2.1 kJ/mol for H2O. For the first time, kinetic polarimetric studies demonstrated differences in the mechanisms of binding of d- and s-element cations to amoxicillin.

Over several months, 14 people were admitted in 6 hospitals with severe symptoms of intoxication with psychoactive substances as a result of mass poisoning. All symptoms occurred after taking a drink that contained crushed phenazepam tablets. Samples of blood (n=10) and urine (n=6) taken from 14 sufferers for forensic, chemical and toxicological examination were analyzed using the HPLC-MS/MS method. Phenazepam was detected in the biomaterial of all 14 patients. Other psychoactive substances (baclofen, pregabalin, chlorprothixene, chlorpromazine, phenibut, tramadol, diazepam), narcotic substances and ethanol were also found in the sufferers. The phenazepam concentration in the blood was in the range of 109.75-786.50 ng/ml, in the urine - 8.97-101.28 ng/ml. The pharmacokinetic and toxicokinetic characteristics of toxicants as well as additional factors characterizing the phenotype of the sufferer in addition to drug's content in the biological material must be taken into account to determine the toxicity level of phenazepam against the background of combined action with other psychoactive substances.

Objective: The objective of this study is to develop methods for identifying herbal medicines and tinctures by processing spectral results across a wide range of wavelengths using principal component analysis (PCA). Methods: Medicinal plants and tinctures of valerian, motherwort, and hawthorn have been analyzed using UV spectrophotometry, spectrofluorimetry, ATR FTIR spectrometry, and X-ray fluorescence spectrometry. PCA was used to process the results of spectral analysis. Statistical processing of spectral results was carried out using the OriginPro program (OriginLab Corporation, USA, 2021). Results: For herbal medicines with sedative, hypotensive, and cardiotonic effects, spectral data libraries have been created in the following dimensions: UV spectrophotometry with 1800 absorption units (Ai), spectrofluorimetry with 4010 fluorescence intensity units (Ii), IR spectroscopy with a light transmittance of 50250 units (Ti), and X-ray fluorescence spectrometry with an intensity of 1568 (Ii). These libraries were used as the primary matrices for PCA. Visualization of the PCA results was done using a scores plot and a loadings plot, which illustrate the contribution of each principal component (PC) to the PCA model. After performing chemometric processing on the original spectral results, it was discovered that samples belonging to the same botanical genus occupy distinct and compact regions in two-dimensional or three-dimensional space. Unknown plant samples (blind samples) and samples of other botanical species were successfully tested using new method. Conclusion: For the first time, tinctures and medicinal plants were identified based on their botanical genus using spectral techniques coupled with principal component analysis, eliminating the need for a chemical reference substance.

The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant Kb (M−1), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery.

The development of affordable and reliable methods for quantitative determination of stable atomic nuclei in aqueous solutions and adjuvant agents used in tumor chemotherapy is an important task in modern pharmaceutical chemistry. This work quantified the deuterium/prothium isotope ratio in aqueous solutions through an original two-dimensional diffuse laser scattering (2D-DLS) software and hardware system based on chemometric processing of discrete interference patterns (dynamic speckle patterns). For this purpose, 10 mathematical descriptors (di), similar to QSAR descriptors, were used. Correlation analysis of bivariate “log di—D/H” plots shows an individual set of multi-descriptors for a given sample with a given D/H ratio (ppm). A diagnostic sign (DS) of differentiation was established: the samples were considered homeomorphic if 6 out of 10 descriptors differed by less than 15% (n ≥ 180). The analytical range (r = 0.987) between the upper (D/H ≤ 2 ppm) and lower (D/H = 180 ppm) limits for the quantification of stable hydrogen nuclei in water and aqueous solutions were established. Using the Spirotox method, a «safe zone» for protozoan survival was determined between 50 and 130 ppm D/H. Here, we discuss the dispersive (DLS, LALLS) and optical properties (refractive index, optical rotation angle) of the solutions with different D/H ratios that define the diffuse laser radiation due to surface density inhomogeneities. The obtained findings may pave the way for the future use of a portable, in situ diffuse laser light scattering instrument to determine deuterium in water and aqueous adjuvants.

Objective: The aim of this study was to demonstrate that chiral switching should be recognized as a widespread phenomenon that extends beyond the production of pure enantiomeric drugs. Methods: To investigate the optical activity of substances from various chemical classes, enantiomers of chiral compounds (Sigma-Aldrich, USA) were chosen: valine and its racemic form (D-valine, L-valine, and racemic valine with optical purity ≥ 99%), L-ascorbic acid (content ≥ 99%), carbohydrates (D-glucose, D-galactose, L-galactose, contents ≥ 99.5%). Solutions were prepared using deuterium-depleted water (DDW–"light" water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), and heavy water (99.9% D2O; Sigma-Aldrich). Optical activity was measured using the Atago POL-1/2 polarimeter. Results: One of the components in the racemic medication mixture can act as an inert agent, exhibit toxicity, or undergo undesirable biotransformation mechanisms, resulting in the formation of products with unknown properties. It has been established that a change in the deuterium/protium (D/H) ratio in water leads to a change in the equilibrium and kinetic characteristics of optically active compounds across various chemical classes, such as amino acids, carboxylic acids, and carbohydrates. An inequality was observed in the absolute values of the optical rotation of the L-and D-isomers of valine and galactose, depending on the D/H isotope ratio. The impact of chiral water clusters on optical rotation accounts for the sudden shift in the specific rotation of dilute solutions (less than 0.5%) of L-ascorbic acid in water, based on the D/H ratio. The influence of the isotopic composition of water was confirmed by studying the temperature-dependent mutarotation kinetics of D-glucose and L-and D-galactose in Arrhenius coordinates. The mutarotation process in natural high-resistivity water is characterized by an activation energy (Ea) of 40.8±1.4 kJ mol-1, while in deuterium-depleted water, Ea = 63.6±3.5 kJ mol-1. This results in a kinetic isotope effect for deuterium (KIED) of 1.6. Conclusion: Methodological approaches have been developed to control chiral switching based on the isotopic composition of water in vivo and in vitro. The study of changes in the optical activity of hierarchical structures in the human body, the influence of solvent properties on the mechanisms of optical rotation, as well as the use of KIED values, can be utilized to monitor various chiral transitions in vitro and living organisms.

Objective: To develop a method for identifying tinctures by assessing their biological activity at different temperatures based on Arrhenius kinetics. Methods: The tinctures of anti-inflammatory and cardiotonic actions were chosen for the Spitotox-test. Chromatographic ethanol (HPLC grade, 99.8%, Fisher Scientific, UK) and deionized high-resistance water (18.2 MΩ cm, Milli-Q, Millipore) were used to prepare 70% water-alcohol extractant. The dispersity of the infusions and solvents was evaluated by LALLS (Malvern, UK) (micrometer range) and DLS (nanometer range) (Zetasizer Nano ZS, Malvern, UK) methods. Results: The observed (obs) values of activation energy ( °bsEa) of ligand-receptor interactions of infusoria Spirostomum ambiguum and components of tinctures with regard to the extractant: water volume ratio was ranked in descending order of toxicity: motherwort (1:10; 87±13 kJ/mol)>calendula (1:7; 103±18 kJ/mol)>eucalyptus (1:7; 159±5 kJ/mol)>valerian (1:5; 135±6 kJ/mol)>hawthorn (1:4; 113±20 kJ/mol). The found values of activation energy were included in the previously created library for the construction of the correlation diagram « °bsEa-LD50», which allowed to assess the toxicity of tinctures in comparison with other pharmaceutical substances. Conclusion: The method for assessing the biological activity of tinctures was developed by Arrhenius kinetics. The values of activation energy °bsEa of ligand-receptor interactions can be used for the identification of tinctures.

Objective: To prove the benefits of biopharmaceutical parameters of cannabinoids over NSAIDs using quantitative structure and activity relationships (QSAR). Methods: The topological indices of Wiener (W) and Balaban (J) were calculated using the previously developed original program ChemicDescript (certificate no. 2003612305). Results: It was shown that the calculated topological indices were in one-to-one correspondence with such biopharmaceutical parameters as the constants of equilibrium binding to cannabinoid receptors CB1 and CB2, toxicity, and lipophilicity. For example, it was shown that when the Wiener index changes from 480 to 530 LogK increases from 1.0 to 3.5. The LD50-W/J and logP-W/J diagrams demonstrate that cannabinoids are less toxic and more lipophilic than NSAIDs. Cannabidiol and cannabinol, having close values of their topological indices and insignificant psychoactivity, have the highest LD50 values, i.e. they are the least toxic. Moreover, for synthetic cannabinoids–nabilone and THJ-2201–the Wiener index is approximately 2 times higher than for plant analogues. Conclusion: In connection with the successful promotion of cannabinoid analgesics in the global pharmaceutical market, the results obtained are important for demonstrating their advantages over NSAIDs in terms of toxicity and lipophilicity. The results demonstrate the possibility of predicting the cannabinoid receptor binding energy of synthetic and newly identified plant cannabinoids, as well as assessing their toxicity and lipophilicity.

The strategy of sustainable industrial development in accordance with “green chemistry” stimulates researchers to search for a “lever” that could provide control over the direction and speed of chemical and biological processes. Water, depleted in deuterium content, is a recognized safe (in contrast to D2O) dissolution medium according to the results of numerous clinical observations. Due to the lower strength of carbon-protium (C-H) chemical bonds compared to carbon-deuterium (C - D), the properties of deuterated compounds, such as the rate of reactions involving them, change. The aim of the work was to study the effect of varying the 21H content on controlling the chemical and biological properties of processes. The highest values of kinetic deuterium isotope effects (KEI), which demonstrated greater sensitivity to the difference in the nucleolar mass D/H in the dissolution medium, correspond to slightly soluble lipophilic molecules. We also found the dependence of the S.ambigua cell biosensor lifetime on the deuterium concentration in the dissolution medium according to the laws of Arrhenius kinetics. Thus, the developed approach based on the laser diffraction technique in controlling the rate of chemical and biological processes can be successfully applied at all stages of the production cycle in the chemical and pharmaceutical industry.

Mechanochemistry is one of the ten great discoveries of green chemistry methods for synthesizing new substances. A drug substance from the fluoroquinolone group was exposed to high-intensity mechanical impacts using a laboratory knife mill for 21 min and constantly monitored by analyzing samples extracted every 3 min with DLS, SLS, LALLS, 2D-LS, optical and digital microscopy, FTIR, and Spirotox methods. A dispersity phenomenon was detected in an area where catastrophic dislocations formed and multiplied via laser methods. The positive correlation between the temperature of deformation and stress was demonstrated, similar to a typical stress–strain curve of a Bochvar–Oding curve and Young’s modulus: the angular coefficient of the straight section to OX was tgα = 10 min−1. Z-Average, ζ-potential, and polydispersity index dependences were represented as discontinuous periodic oscillations analogous to the defect and impurity transitions near the dislocation core. Deformation r from the high-intensity mechanical impact resulted in covalent bonds showing hyper- and hypochromic effects under FTIR spectra, a bathochromic shift of the maximum, and an oscillation emission at 3240 cm−1. A 2D-LS fingerprint diagram obtained via the topological convolution of the light scattering matrix made it possible to distinguish the off-loading samples from the native substance. The investigation of the dissolution kinetics in water via laser diffraction led to conclusions about the limiting diffusion stage and the acceleration of the mechanoactivation of the solid body’s dissolution under both linear and plastic deformation. The acceleration of obsEa of the cell death process in the temperature range from 296 to 302 K indicated a significant (2.5-fold) decrease in the toxicity of the aqueous 9 mM (1:3) sample solution at 21 min compared to that of the native levofloxacin. Adherence to the mechanochemistry laws provides an opportunity for drug repositioning to change their brand status by identifying new physicochemical and biological properties.

Objective. To develop the basics of technology for X-ray fluorescence determination of silver in colloidal solutions. Relevance. Silver preparations are interesting as an alternative to antibiotics. Сurrently on the pharmaceutical market there is a large number of silver-containing colloidal dietary supplements, 70% of which contain silver in ionic form. The energy dispersive method of X-ray fluorescence analysis is an express method without long-term sample preparation. Materials and methods. Silver proteinate (8% Ag), Sigma-Aldrich; ProtargolLor (P.J.S.C. “Pharmstandard”, Kursk); Sialor (J.S.C. RENEWAL®); Argitos colloidal silver (“Nanosphere”, Russia), Argent Colloidal (Nutri expert, France). Dual Laser Light Scattering 2D-DLS (Zetasizer Malvern). Energy dispersive spectrometer Shimadzu EDX-7000 (Japan); OriginLab Corporation, USA. Results. The technology of the X-ray fluorescence determination of silver in colloidal solutions from various companies was described in this paper. The present study has exploited the energy dispersive spectrometer Shimadzu EDX-7000 (Japan). The fluorescence intensity at AgKα = 22.105 keV depends linearly on the silver concentration in the range of 0.01% - 1% according to the equation I = (5.1 ± 0.1) · СAg for silver nitrate and I = (1.64 ± 0.03) · CAg for silver proteinate, which is due to the effect of the organic matrix. Conclusion. The new XRF method was applied for quality control of protargol and other Ag-containing drugs and parapharmaceuticals.

It has recently been shown that the titer of the SARS-CoV-2 virus decreases in a cell culture when the cell suspension is irradiated with electromagnetic waves at a frequency of 95 GHz. We assumed that a frequency range in the gigahertz and sub-terahertz ranges was one of the key aspects in the “tuning” of flickering dipoles in the dispersion interaction process of the surfaces of supramolecular structures. To verify this assumption, the intrinsic thermal radio emission in the gigahertz range of the following nanoparticles was studied: virus-like particles (VLP) of SARS-CoV-2 and rotavirus A, monoclonal antibodies to various RBD epitopes of SARS-CoV-2, interferon-α, antibodies to interferon-γ, humic–fulvic acids, and silver proteinate. At 37 °C or when activated by light with λ = 412 nm, these particles all demonstrated an increased (by two orders of magnitude compared to the background) level of electromagnetic radiation in the microwave range. The thermal radio emission flux density specifically depended on the type of nanoparticles, their concentration, and the method of their activation. The thermal radio emission flux density was capable of reaching 20 μW/(m2 sr). The thermal radio emission significantly exceeded the background only for nanoparticles with a complex surface shape (nonconvex polyhedra), while the thermal radio emission from spherical nanoparticles (latex spheres, serum albumin, and micelles) did not differ from the background. The spectral range of the emission apparently exceeded the frequencies of the Ka band (above 30 GHz). It was assumed that the complex shape of the nanoparticles contributed to the formation of temporary dipoles which, at a distance of up to 100 nm and due to the formation of an ultrahigh strength field, led to the formation of plasma-like surface regions that acted as emitters in the millimeter range. Such a mechanism makes it possible to explain many phenomena of the biological activity of nanoparticles, including the antibacterial properties of surfaces.

Objective: To substantiate the possibility of using polarimetry to control the quality of tinctures as an additional pharmacopoeial method. Methods: The polarimetric method (POL-1/2, Atago, Japan, the measurement accuracy of±0.002 °) was used to measure the optical activity (α °) of motherwort, valerian and hawthorn tinctures. The dynamic light scattering method (DLS; Zetasizer Nano ZS, Malvern, UK) was used to assess the stability of alcoholic and aqueous dilutions of tinctures according to the intensity of dynamic light scattering dependent on the size (d, nm) of the dispersed phase particles and the values of the electrokinetic potential (ξ, mV). Results: For the first time in this investigation, the polarimetry approach was proposed to evaluate the cardiotonic and hypotensive tinctures' quality and for their identification. Valerian tincture, dilution 1:40,-0.10°<α°<-0.89°; motherwort, tincture-dilution 1:10,-0.10°<α°<-2.21°; hawthorn, tincture without dilution,-0.76°<α°<-1.55°-these are the acceptable ranges of optical activity (α°) of their alcohol dilutions. Beyond these intervals, the use of the polarimetric approach is impossible. Values of optical activity below 0.1 correspond to too low a content of optically active components. Tinctures with optical activity above the upper value of the interval were unstable dispersed systems with low values of the electrokinetic potential (|ξ|≪25mV) and micron particle sizes. Reference tinctures were made from raw materials (Leonurus cardiaca L.) to verify the results. The quality parameters: optical activity (α°), spectra of dynamic light scattering by intensity, volume, and number ("I-d"; "V-d"; "N-d"), electrokinetic potential (ξ) values, and photon pulse count per second (Count Rate, kcps) corresponded to the results obtained for pharmaceutical dosage forms. Conclusion: The permissible intervals of optical activity (α°) of their ethanol dilutions, as well as their relationships with the particle size of the dispersed phase and the values of the electrokinetic potential, were established for the first time to evaluate the quality of tinctures. The obtained results show that polarimetry can be recommended as an additional pharmacopoeial quality control method for tinctures.

Introduction. The production, standardization and quality control process of various dietary supplements containing chelated zinc requires validated quantitative assessment methods. In this work, we propose an X-ray fluorescence spectroscopy (XRF) technique for determining the zinc content in the composition of coordination compounds using the example of a synthesized chelate complex with methionine. Aim. To synthesize Zn(Met) 2 chelate complex, to develop and validate a method for its quantitative analysis using the XRF method. Materials and methods . The synthesized zinc chelate complex was investigated by IR spectroscopy. The XRF method was used to develop a method for quantifying the zinc content in the synthesized complex. We used dry mixtures of zinc sulfate monohydrate and L-methionine (Met) in a molar ratio of Zn to Met – 1 : 1, 1 : 2, 1 : 4, 1 : 8 and 1 : 16 and also aqueous solutions of zinc sulfate and L-methionine in a molar ratio of Zn to Met 1 : 2 with Zn concentrations from 0.5 to 100 mmol/l as calibration standards. Complexometric titration was used as an arbitration method for the quantitative determination of zinc content in the samples under study. Results and discussion . The IR spectrum of chelate complex confirmed the presence of a donor-acceptor bond between Zn 2+ and the nitrogen atom of amino group in methionine. The titration results showed chelate compounds have a composition corresponding to the stoichiometric formula Zn(Met) 2 . XRF analysis of dry standard mixed samples demonstrated the presence of matrix effect, that makes impossible an accurate assessment of zinc content in the chelate compound. According to the XRF spectra of aqueous solutions containing zinc sulfate and methionine in a ratio of 1 : 2 at a zinc concentration of 0.5; 1; 2; 3; 4; 5; 10; 25; 50 and 100 mmol/L, a calibration graph was constructed – the dependence of the fluorescence signal intensity for the Kα line of zinc on the concentration of zinc in the solution (r = 0.9996). The method was evaluated by the following validation parameters: specificity, linearity, correctness, precision, and analytical range. The specificity of the validated method was proven in the presence of copper, iron, and silver. Conclusion . The developed method make it possible to determine with sufficient precision and correctness the content of Zn 2+ in its aqueous solutions of inorganic and organic nature by the XRF method in the concentration range from 3 to 100 mmol/l without the influence of the matrix.

The most important task in the design of dosage forms is to modify the pharmaceutical substances structure in order to increase solubilization, targeted delivery, controlled rate of drug administration, and its bioavailability. Screening—laboratory (in vitro) or computer (in silico)—as a procedure for selecting a prototype for the design of a drug molecule, involves several years of research and significant costs. Among a large number of solvents and diluents (alcohol, ether, oils, glycerol, Vaseline) used in the pharmaceutical industry for the manufacture of drugs water finds the greatest application. This is because all biological reactions (reactions in living systems) take place in water and distribution of the fluid in the body and the substances found within is critical for the maintenance of intracellular and extracellular functions. Modern studies in the field of the stable isotopic compositions of natural water and its structure and properties make it possible to use isotopic transformations of the water to improve the pharmacokinetic properties of medicinal substances without previous structural modification. It is known that by replacing any of the atoms in the reacting substance molecule with its isotope, it is possible to record changes in the reactivity, which are expressed as a change in the reaction rate constant, i.e., in the manifestation of the kinetic isotope effect (KIE). The article presents the results of studies on the effect of the kinetic isotope effect of a solvent—water—on increasing the solubility and dissolution rate constants of poorly soluble drugs using laser diffraction spectroscopy. The results of the studies can be successfully implemented in pharmaceutical practice to overcome the poor solubility of medicinal substances of classes II and IV, according to the biopharmaceutical classification system (BCS), in water for pharmaceutical purposes by performing its preliminary and safe isotopic modification.

Objective: To evaluate the biological activity of chemical peeling substances based on enzymatic and Arrhenius kinetics using Spirostomum ambiguum as an alternative approach to animal experiments. Methods: The Spirotox method was used to analyze the mechanism of «xenobiotic-cell» interaction, similar to the Michaelis-Menten enzymatic kinetics. The Hill-Langmuir equation was used to determine the degree of cooperativity in the binding of xenobiotics to cellular receptors. Using the Arrhenius kinetics, the observed activation energy obsEa of cell death in the model solutions of glycolic and carbolic acids was determed, which will allow predicting the toxicity parameters of any peeling substances. Results: The relationship Spirostomum ambiguum lifetime tL-lgC concentration of peeling compound solution made it possible to characterize the moment of cellular transition from the intermediate state C•Ln to the dead state DC, characterized by irreversible structural and functional changes in the cell/death. The values were 5.3 mmol•l-1 for glycolic acid solutions and 2.8 mmol•l-1 for carbolic acid solutions. Equilibrium constants Keq of complexation, the rate of infusoria death fm, and the degree of ligand cooperativity n were calculated. The activation energy °bsEa of cell death was determined in Arrhenius coordinates, which were 210±0.39 kJ·mol-1 and 108±0.09 kJ·mol-1 for glycolic and carbolic acids respectively. The correlation between the values ​​of activation energy and DL50 of mammals (rats) was discovered. Conclusion: The obtained kinetic parameters made it possible, without animals and humans testing, to characterize the mechanisms of interaction of peeling substances with the living cell.