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A Gridded Electron Gun for a Sheet Beam Klystron
This paper describes the development of an electron gun for a sheet beam klystron. Initially intended for accelerator applications, the gun can operate at a higher perveance than one with a cylindrically symmetric beam. Results of 2D and 3D simulations are discussed
Numerical Simulation of the Medical Linear Accelerator Electron Beams Absorption by ABS-Plastic doped with Metal
In this paper the numerical simulation results of the dose spatial distribution of the medical electron beams in ABS-plastic doped with different concentrations of lead and zinc are shown. The dependences of the test material density on the lead and zinc mass concentrations are illustrated. The depth dose distributions of the medical electron beams in the modified ABS-plastic for three energies 6 MeV, 12 MeV and 20 MeV are tested. The electron beam shapes in the transverse plane in ABS-plastic doped with different concentrations of lead and zinc are presented
Approaches to Pharmaceutical Analysis of Modern Peptide and Oligonucleotide Products as Illustrated by a Small Interfering RNA-Based Novel Therapeutic for the Treatment of Bronchial Asthma
Methods used to control the quality of peptide products depend on the level of development of analytical and bioorganic chemistry, and the level of instrumentation. Peptide identification is a difficult task and largely depends on the complexity of its structure. There does not exist a comprehensive and simple test, except for NMR, which, however, is rather expensive and time-consuming and involves complex data interpretations. Moreover, it does not allow for unambiguous determination of the peptide purity and formula (amino acid composition, sequence, chirality of amino acid residues). For this reason, a combination of methods is often used, including amino acid analysis, TLC/HPLC and mass spectrometry, and, less frequently, sequencing. Current international practice of peptide analysis is to use HPLC in combination with mass spectrometric, mainly tandem (HPLC-MS/MS), detection. According to literature sources the amino acid sequence of linear peptides can be analysed using various enzymes and subsequent identification of proteolysis products by mass spectrometry. This article presents approaches to the development of test methods for analysis of purity and identification testing of a small interfering RNA-based novel medicinal product, which will help standardise and control the quality of the production process
Comparative study of perindopril and perindopril metabolite pharmacokinetics using the HPLC/MS method
Perindopril is a prodrug which is converted to an active metabolite perindoprilat in the human organism. The present study led to the development of a fast and easily reproducible procedure for simultaneous detection of perinoprilat and its metabolite in plasma using HPLC with mass-spectrometric detector (LC-MS). Detection of the target substance was performed using atmospheric pressure electrospray ionization (API-ES) techniques in negative polarity in two modes: SIM1, ion, m/z=368,10 for perindopril and SIM2, ion, m/z=339,30 for perindoprilat. Retention time of perindopril was about 2,4 min, for perindoprilat - about 1,4 min. Sample processing was performed using solid-phase extraction. The methodβs limit of quantification was equal to 1 ng/ml for perindopril and 1 ng/ml for perindoprilat. The developed procedure was used to analyse pharmacokinetics and bioequivalence of medicines containing 8 mg of perindopril. Values of all calculated pharmacokinetic parameters had no statistically meaningful differences. Confidence intervals obtained fall within bioequivalence criterion (80-125% for AUC and 75-133% for Π‘max ΠΈ Cmax/AUC). The medicines under analysis were found to be bioequivalent
Analysis of Pharmacokinetic Parameters of Acetylsalicylic Acid for Prediction of Potential Nephrotoxic Effects
Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acidβsalicylic acidβin blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mmΓ150 mm; 5.0 ΞΌm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-β (total area under the pharmacokinetic curve from 0 to β), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 Β± 0.5 h, Cmax was 4523.0 Β± 725.0 ng/mL, and Tmax was 0.98 Β± 0.4 h. AUC0βt was equal to 16183.0 Β± 3823.0 ngΓh/m, Vd/F was 12.0 Β± 3.1 L/kg, and MRT was 2.9 Β± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug
Comparative Dissolution Kinetics of Several Multisource Thioctic Acid Products
The relationship between dissolution and bioavailability is an example of the interdependency between the quality of a medicinal product and its safety and efficacy. The uniqueness of thioctic acid is that it can exist in an oxidised and a reduced form, showing lipophilic (lipoic acid) and hydrophilic (dihydrolipoic acid) properties. Bioavailability studies of thioctic acid are necessary to evaluate the expected therapeutic effect and mitigate side effects of the medicinal product.The aim of the study was to carry out equivalence dissolution testing to compare the release of thioctic acid from medicinal products produced by several manufacturers.Materials and methods: the study used a reference medicinal product and three multisource medicinal products by different manufacturers; more specifically, film-coated tablets containing 600 mg of thioctic acid. The experiment was carried out in dissolution media at pH of 6.8Β±0.05 and 1.2Β±0.05. Statistical analysis was performed by calculating the average amounts of the substance dissolved, the standard deviation (SD), and the relative standard deviation (RSD, %) using Microsoft Office Excel 2007.Results: The authors chose the testing conditions (dissolution media pH values of 6.8Β±0.05 and 1.2Β±0.05) taking into account the nature and characteristics of thioctic acid. The comparison of thioctic acid release profiles based on the calculation of the similarity factor (f2) showed that the dissolution profiles of multisource medicinal products 2 and 3 at pH 6.8 were equivalent to that of the reference medicinal product (more than 85% of the active pharmaceutical ingredient released within 15 minutes) and the dissolution profile of multisource medicinal product 1 was not equivalent to it (with f2 of 28).Conclusions: the established differences in the rate and degree of active ingredient release from the studied medicinal products may indicate possible differences in their pharmacological effectiveness in vivo
Retargeted adenoviruses for radiation-guided gene delivery
The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78βkDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment
The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells
ΠΠ½Π°ΡΠ΅Π½ΠΈΠ΅ ΡΠ΅Π΄ΠΎΠΊΡ-ΡΡΠ°ΡΡΡΠ° ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q10 ΠΊΠ°ΠΊ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠ° ΠΎΠΊΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΡΡΠ΅ΡΡΠ°
The article examines the role of ubiquinone as a redox molecule whose functions consist in electron transport in the mitochondrial respiratory chain and regeneration of endogenous antioxidants. Changes in electron redox pathways cause uncontrolled release of reactive oxygen species, which leads to oxidative stress and development of pathologies. The objective of the study was to determine the content of coenzyme Q10 and its redox status in the human body as a biomarker of oxidative stress in various pathologies. This was achieved by assessing and consolidating data on changes in concentrations of the oxidized, reduced ubiquinone forms and total ubiquinone in various pathologies. Total serum ubiquinone was reduced in patients with chronic heart failure (0.68 ΞΌmol/L) compared with the control group (0.97 ΞΌmol/L). The redox status, expressed as the [ubiquinol]/ [ubiquinone] concentration ratio, decreased in patients with coronary heart disease (0.49 Β± 0.34), diabetes (0.26 Β± 0.16) compared with the healthy subjects (1.23β1.41). A negative correlation with malonic dialdehyde was observed. The authors analysed the possibility of assessing the efficacy of statin therapy by plasma ubiquinone concentration in patients. Patients with hyperlipidemia who received statins showed a statistically significant reduction in ubiquinol concentration after taking the drug (from 0.81 to 0.46 ΞΌg/mL) and the [ubiquinone]/[total ubiquinone] ratio (from 11 to 10 %), which confirms the potential mechanism of statinassociated muscle injury development. Thus, coenzyme Q10 redox status, as well as the concentrations of oxidized, reduced and total ubiquinone can be effective biomarkers of oxidative stress in cardiovascular diseases, diabetes, as well as an important indicator in evaluating the efficacy of hyperlipidemia treatment.Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Π° ΡΠΎΠ»Ρ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½Π° ΠΊΠ°ΠΊ ΡΠ΅Π΄ΠΎΠΊΡ-ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ, ΡΡΠ½ΠΊΡΠΈΡΠΌΠΈ ΠΊΠΎΡΠΎΡΠΎΠΉ ΡΠ²Π»ΡΡΡΡΡ ΠΏΠ΅ΡΠ΅Π½ΠΎΡ ΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΎΠ² Π² Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠ΅ΠΏΠΈ ΠΌΠΈΡΠΎΡ
ΠΎΠ½Π΄ΡΠΈΠΈ ΠΈ ΡΠ΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΡ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
Π°Π½ΡΠΈΠΎΠΊΡΠΈΠ΄Π°Π½ΡΠΎΠ². ΠΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠ΅Π΄ΠΎΠΊΡ-ΠΏΡΡΠ΅ΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΠ½ΠΎΠ² Π²ΡΠ·ΡΠ²Π°Π΅Ρ Π½Π΅ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΡΡ Π²ΡΡΠ°Π±ΠΎΡΠΊΡ Π°ΠΊΡΠΈΠ²Π½ΡΡ
ΡΠΎΡΠΌ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π°, ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΎΠΊΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌΡ ΡΡΡΠ΅ΡΡΡ ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q10 ΠΈ Π·Π½Π°ΡΠ΅Π½ΠΈΡ Π΅Π³ΠΎ ΡΠ΅Π΄ΠΎΠΊΡ-ΡΡΠ°ΡΡΡΠ° Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅ ΠΊΠ°ΠΊ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠ° ΠΎΠΊΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΡΡΠ΅ΡΡΠ° ΠΏΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΡ
, Π΄Π»Ρ ΡΠ΅Π³ΠΎ Π±ΡΠ»ΠΈ ΠΎΡΠ΅Π½Π΅Π½Ρ ΠΈ ΠΎΠ±ΠΎΠ±ΡΠ΅Π½Ρ Π΄Π°Π½Π½ΡΠ΅ ΠΎ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ ΠΎΠΊΠΈΡΠ»Π΅Π½Π½ΠΎΠΉ, Π²ΠΎΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΠΎΠΉ ΡΠΎΡΠΌΡ ΠΈ ΠΎΠ±ΡΠ΅Π³ΠΎ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½Π° ΠΏΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΡ
. Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ ΠΎΠ±ΡΠ΅Π³ΠΎ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½Π° Π² ΡΡΠ²ΠΎΡΠΎΡΠΊΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ Π±ΡΠ»ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΎ (0,68 ΠΌΠΊΠΌΠΎΠ»Ρ/Π») ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΠΎΠΉ Π³ΡΡΠΏΠΏΠΎΠΉ (0,97 ΠΌΠΊΠΌΠΎΠ»Ρ/Π»). Π Π΅Π΄ΠΎΠΊΡ-ΡΡΠ°ΡΡΡ, Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΉ ΠΊΠ°ΠΊ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ [ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ»]/[ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½], ΡΠ½ΠΈΠΆΠ°Π»ΡΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π±ΠΎΠ»Π΅Π·Π½ΡΡ ΡΠ΅ΡΠ΄ΡΠ° (0,49 Β± 0,34), Π΄ΠΈΠ°Π±Π΅ΡΠΎΠΌ (0,26 Β± 0,16) ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ ΡΠΎ Π·Π΄ΠΎΡΠΎΠ²ΡΠΌΠΈ Π»ΠΈΡΠ°ΠΌΠΈ (1,23β1,41). ΠΡΠΈ ΡΡΠΎΠΌ Π½Π°Π±Π»ΡΠ΄Π°Π»Π°ΡΡ ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½Π°Ρ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΡ Ρ ΠΌΠ°Π»ΠΎΠ½ΠΎΠ²ΡΠΌ Π΄ΠΈΠ°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠΌ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠ°ΡΠΈΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΠΎ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½Π° Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². Π£ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π³ΠΈΠΏΠ΅ΡΠ»ΠΈΠΏΠΈΠ΄Π΅ΠΌΠΈΠ΅ΠΉ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΡΠ°ΡΠΈΠ½Ρ, Π±ΡΠ»ΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½Ρ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ»Π° ΠΏΠΎΡΠ»Π΅ ΠΏΡΠΈΠ΅ΠΌΠ° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° (Ρ 0,81 Π΄ΠΎ 0,46 ΠΌΠΊΠ³/ΠΌΠ») ΠΈ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ [ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½]/[ΠΎΠ±ΡΠΈΠΉ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½] (Ρ 11 Π΄ΠΎ 10 %), ΡΡΠΎ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π΅Ρ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠΉ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ ΡΡΠ°ΡΠΈΠ½-Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠΉ ΠΌΡΡΡ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΠ΅Π΄ΠΎΠΊΡ-ΡΡΠ°ΡΡΡ ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q10, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΠΎΠΊΠΈΡΠ»Π΅Π½Π½ΠΎΠ³ΠΎ, Π²ΠΎΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈ ΠΎΠ±ΡΠ΅Π³ΠΎ ΡΠ±ΠΈΡ
ΠΈΠ½ΠΎΠ½Π° ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠ°ΠΌΠΈ ΠΎΠΊΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΡΡΠ΅ΡΡΠ° ΠΏΡΠΈ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ
, Π΄ΠΈΠ°Π±Π΅ΡΠ΅, Π° ΡΠ°ΠΊΠΆΠ΅ Π²Π°ΠΆΠ½ΡΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΌ ΠΏΡΠΈ ΠΎΡΠ΅Π½ΠΊΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ Π³ΠΈΠΏΠ΅ΡΠ»ΠΈΠΏΠΈΠ΄Π΅ΠΌΠΈΠΈ
ΠΠΎΠ΄Ρ ΠΎΠ΄ ΠΊ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΌΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ Π²Π΅ΡΠ΅ΡΡΠ² Π² Π±ΠΈΠΎΠΆΠΈΠ΄ΠΊΠΎΡΡΡΡ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°ΠΏΠΏΠ°ΡΠ°ΡΠ°
Relevance of the study: The quantification of endogenous substances is an important task in experimental and clinical pharmacology. In the case of working with endogenous compounds, certain difficulties arise. The main one is the impossibility of obtaining the same biomatrix without endogenous compounds for use as standard solutions in the construction of calibration curves.Β Purpose: The aim of our study was to develop a mathematical methodology for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows us to obtain a statistically reliable interval estimation of the concentration of endogenous compounds.Β Materials and methods: To implement the computational part of the proposed algorithm, the Mathcad engineering calculation program version 15.0 from PTC (Parametric Technology Corporation) is used, which operates under the family of Windows operating systems (XP, 7, Vista, 8).Β Main results: A mathematical methodology has been developed for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows one to obtain a statistically reliable interval estimate of the concentration of endogenous compounds. A feature of this technique is the use of an exclusively analyzed bioobject for quantitative determination of endogenous substances, without the use of so-called βpureβ bioobjects for calibration curves, as well as expensive deuterated analogs of markers β substrates of CYP450 isoenzymes and their metabolites. This allows you to maintain the original biomatrix effect when removing the chromatogram. A statistical apparatus is also used to eliminate possible gross errors. To confirm the reliability of the developed method of quantitative determination, the convergence of the results obtained by this method using deuterated standards is established.Β Conclusions: A mathematical methodology has been developed for calculating the concentration of endogenous compounds in biological objects measured by chromatography, which allows one to obtain a statistically reliable interval estimate of the concentration of endogenous compounds. A feature of this technique is the use of only the analyzed bioobject for quantitative determination of endogenous substances, which allows you to maintain the original biomatrix effect when removing the chromatogram.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΠΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ Π²Π°ΠΆΠ½ΠΎΠΉ Π·Π°Π΄Π°ΡΠ΅ΠΉ Π² ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ. Π ΡΠ»ΡΡΠ°Π΅ ΡΠ°Π±ΠΎΡΡ Ρ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡΠΌΠΈ Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ½Π½ΡΠ΅ ΡΠ»ΠΎΠΆΠ½ΠΎΡΡΠΈ. ΠΠ»Π°Π²Π½ΡΠΌ ΠΈΠ· Π½ΠΈΡ
ΡΠ²Π»ΡΠ΅ΡΡΡ Π½Π΅Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ°ΠΊΠΎΠΉ ΠΆΠ΅ Π±ΠΈΠΎΠΌΠ°ΡΡΠΈΡΡ Π±Π΅Π· ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π΄Π»Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΡΡΠ°Π»ΠΎΠ½Π½ΡΡ
ΡΠ°ΡΡΠ²ΠΎΡΠΎΠ² ΠΏΡΠΈ ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΠΈ ΠΊΠ°Π»ΠΈΠ±ΡΠΎΠ²ΠΎΡΠ½ΡΡ
ΠΊΡΠΈΠ²ΡΡ
.Β Π¦Π΅Π»Ρ: Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΡΠ°ΡΡΡΡΠ° ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π² Π±ΠΈΠΎΠΎΠ±ΡΠ΅ΠΊΡΠ°Ρ
Ρ ΠΏΠΎΠΌΠΎΡΡΡ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ², ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΠ΅ΠΉ ΠΏΠΎΠ»ΡΡΠΈΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΡΠ½ΡΡ ΠΎΡΠ΅Π½ΠΊΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ.Β ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ: Π΄Π»Ρ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π²ΡΡΠΈΡΠ»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠ°ΡΡΠΈ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ Π°Π»Π³ΠΎΡΠΈΡΠΌΠ° ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΡΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠ° ΠΈΠ½ΠΆΠ΅Π½Π΅ΡΠ½ΡΡ
ΡΠ°ΡΡΡΡΠΎΠ² Mathcad Π²Π΅ΡΡΠΈΠΈ 15.0.Β Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΡΠ°ΡΡΡΡΠ° ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π² Π±ΠΈΠΎΠΎΠ±ΡΠ΅ΠΊΡΠ°Ρ
Ρ ΠΏΠΎΠΌΠΎΡΡΡ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ², ΠΊΠΎΡΠΎΡΠ°Ρ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΠΎΠ»ΡΡΠΈΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΡΠ½ΡΡ ΠΎΡΠ΅Π½ΠΊΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ. ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΡ Π΄Π°Π½Π½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ Π±ΠΈΠΎΠΎΠ±ΡΠ΅ΠΊΡΠ° Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ², Π±Π΅Π· ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ°ΠΊ Π½Π°Π·ΡΠ²Π°Π΅ΠΌΡΡ
Β«ΡΠΈΡΡΡΡ
Β» Π±ΠΈΠΎΠΎΠ±ΡΠ΅ΠΊΡΠΎΠ² Π΄Π»Ρ ΠΊΠ°Π»ΠΈΠ±ΡΠΎΠ²ΠΎΡΠ½ΡΡ
ΠΊΡΠΈΠ²ΡΡ
, Π° ΡΠ°ΠΊΠΆΠ΅ Π΄ΠΎΡΠΎΠ³ΠΎΡΡΠΎΡΡΠΈΡ
Π΄Π΅ΠΉΡΠ΅ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² β ΡΡΠ±ΡΡΡΠ°ΡΠΎΠ² ΠΈΠ·ΠΎΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ² CYP450 ΠΈ ΠΈΡ
ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΡΠΎΠ². ΠΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠΎΡ
ΡΠ°Π½ΠΈΡΡ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΠΉ Π±ΠΈΠΎΠΌΠ°ΡΡΠΈΡΠ½ΡΡ
ΡΡΡΠ΅ΠΊΡ ΠΏΡΠΈ ΡΠ½ΡΡΠΈΠΈ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΠΌΠΌΡ. Π’Π°ΠΊΠΆΠ΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΡΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°ΠΏΠΏΠ°ΡΠ°Ρ Π΄Π»Ρ ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΡ
Π³ΡΡΠ±ΡΡ
ΠΎΡΠΈΠ±ΠΎΠΊ. ΠΠ»Ρ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½ΠΈΡ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎΡΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° ΡΡ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
Π΄Π°Π½Π½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈ ΠΏΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π΅ΠΉΡΠ΅ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΡΠ°Π½Π΄Π°ΡΡΠΎΠ².Β ΠΡΠ²ΠΎΠ΄Ρ: Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΠΌΠ°ΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° ΡΠ°ΡΡΡΡΠ° ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π² Π±ΠΈΠΎΠΎΠ±ΡΠ΅ΠΊΡΠ°Ρ
Ρ ΠΏΠΎΠΌΠΎΡΡΡ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ², ΠΊΠΎΡΠΎΡΠ°Ρ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΠΎΠ»ΡΡΠΈΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΡΠ½ΡΡ ΠΎΡΠ΅Π½ΠΊΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ.
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