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The method of express detection of hypotensive drugs (atenolol, propranolol, nifedipine, enalaprile and verapamil) in urine samples of patients with acute poisonings was developed. The optimum conditions of group identification of hypotensive drugs using TLC were found. Analysis by GC-MS allows to detect both the native substances and their metabolites. The developed method of analysis of antihypertensive drugs can be used for the diagnosis of acute poisoning.

Vancomycin is prescribed to patients in serious condition with infections caused by Gram-positive microorganisms; however, if the therapeutic plasma concentration of the medicinal product is exceeded, it can have a nephrotoxic effect.The aim of the study was to demonstrate the possibility of using therapeutic drug monitoring (TDM) to reduce the risk of developing nephropathy in intensive care unit patients with sepsis.Materials and methods: the study comprised a retrospective analysis of four clinical cases of patients with sepsis admitted to intensive care units of I.V. Davydovsky City Clinical Hospital in 2021 and treated with vancomycin. TDM of vancomycin plasma levels was performed by reverse-phase high-performance liquid chromatography with mass spectrometric detection.Results: using the four cases of septic patients, the study demonstrated that vancomycin at adequate case-specific doses may result in plasma concentrations beyond the therapeutic range. TDM of vancomycin concentrations helped to prevent further deterioration of renal dysfunction in one septic patient having developed acute kidney injury and to control the achievement of therapeutic vancomycin concentrations or timely adjust the dose to that effect in the other three cases.Conclusions: a timely correction of vancomycin dosing with plasma TDM allows for achieving high antimicrobial efficacy in patients with sepsis and minimising the nephrotoxic effect of the medicinal product. Studies of the feasibility of using TDM as a treatment personalisation tool for patients in serious condition will continue in the future.

Aim. To investigate on post-COVID period in patients of the Eurasian region.Material and methods. A total of 9364 consecutively hospitalized patients were included in ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to ACTIV register, 63% of patients after COVID-19 had new adverse symptoms or exacerbations of the existing symptoms lasting for up to 1 year. After hospital discharge, 79,8% of patients sought unscheduled medical attention in the first 3 months, 79,1% at 4-6 months, and 64,8% at 7-12 months. Readmission rate was 11,8% in the first 3 months, 10,9% at 4-6 months, and 10,1% at 7-12 months. The most common reasons for unscheduled treatment in the first 3 months were uncontrolled hypertension, decompensated type 2 diabetes, destabilization of coronary artery disease, gastrointestinal disease, AF episodes, exacerbation of asthma and chronic obstructive pulmonary disease, decompensated heart failure (HF). The 12-month mortality of COVID-19 survivors after the discharge was 3,08%. Multivariate analysis showed that independent risk factors for fatal outcome were age (direct correlation), the levels of hemoglobin (inverse correlation), oxygen saturation (inverse correlation), and aspartate aminotransferase (direct correlation), as well as class III-IV HF, prior stroke, cancer, inhospital acute kidney injury. Based on these identified risk factors, a nomogram was constructed to determine the 3-month mortality risk after discharge.Conclusion. Analysis of ACTIV register showed that end of the acute phase of COVID-19 does not imply a complete recovery.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of

Relevance The large number of atypical antipsychotic drugs on the market , the breadth of their medical and non-medical use, and their relative affordability make atypical antipsychotics common causes of overdose, suicidal actions or non-medical use of drugs. At the same time, they remain insufficiently studied from the chemical and toxicological point of veiw.Aim od study: creation of available express method of detection of clozapine, olanzapine, quetiapine and risperidone in the urine of patients with acute poisoning.Material and methods Thin layer chromatography (TLC), gas chromatography with mass selective detection (GC-MS), and high performance liquid chromatography with mass selective detection (HPLC-MS/MS) were used. The preparation of intact urine samples with addition of standard solutions of clozapine, olanzapine, quetiapine, risperidone and urine samples of patients with symptoms of acute poisoning with given drugs was carried out by methods of liquid-liquid extraction at alkaline pH values for TLC chloroform, a mixture of ethyl acetate-diethyl ether (1:1) for GC-MS and acetonitrile for HPLC-MS/MS.Results A TLC method has been developed to detect clozapine, olanzapine, quetiapine and risperidone, which allows its the presence to be quickly revealed in the patient’s urine at the preliminary examination stage and also distinguish them from each other in case of the same type of symptoms of poisoning. For confirmatory analysis, it is advisable to use the methods of HPLC-MS/MS and GC-MS. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment and allows clozapine, olanzapine, quetiapine and risperidone to be differentiated from other toxicologically significant psychoactive substances found in general screening.

Introduction. Vitex agnus-castus is an important plant in medicine. Extract from its fruits is used as part of drugs for the treatment of premenstrual syndrome.Aim. To study the chemical composition of water-ethanol extract from Vitex fruits, to establish the dopaminergic activity of various extract fractions separated by lipophilicity, as that of its dominant iridoid-agnusideMaterials and methods. The composition of water-ethanol extraction was studied using HPLC-UV and HPLC-MS/MS methods. Identification of the extract components was performed by comparing the retention times on the chromatograms of the test and standard samples. The extract and its fractions were analyzed in vitro using the tyrosine hydroxylase biotest system. Cyclodinone® (oral drops, Vitex agni casti fructuum extract) was used as a reference drug.Results and discussion. Protocatechuic acid, chlorogenic acid, p-hydroxybenzoic acid, agnuside, mizodendron, 6'-O-p-hydroxybenzoylmusaenoside acid, luteolin-7-glucoside, 5-O-caffeoylquinic acid, vitexin, luteolin, apigenin, maslinic acid, corosolic acid and linolenic acid were identified. The liquid extract obtained in the laboratory showed the same activity as Cyclodinone®, ethyl acetate fraction, and agnuside.Conclusion. This work is the most extensive study of the vitex fruit in relation to the nomenclature of identified compounds. The total extract was shown to be more active than any of its fractions proving the synergistic effect of the extract components on the dopamine neurotransmitter system. This observation justifies the feasibility of using the total extract of the vitex fruit. In vitro agnuside demonstrates high dopaminergic activity. This makes it possible to standardize the extract and medicinal plant materials according to the agnuside content.

Rational use of glybenclamide products in the treatment of patients with type 2 diabetes remains a high-priority task. The paper offers a summary of the main groups of glibenclamide drugs and describes pharmacogenetics of glybenclamide. Glibenclamide is metabolized by the enzyme cytochrome P450 2C9 (CYP2C9). Individuals with genetically determined low CYP2C9 activity are at an increased risk of hypoglycaemia. Carriers of CYP2C9*3 and CYP2C9*2 alleles tend to have higher concentrations of glybenclamide in blood and increased insulin secretion. Pharmacogenetic testing of patients and drug concentration monitoring using HPLC-MS can help reduce the risk of hypoglycemia during glibenclamide treatment. Based on literature review the authors selected the method characterised by a simple sample preparation procedure, short analysis time, and a wide analytical range for the substances being determined. This method can be useful both for bioequivalence studies and evaluation of glibenclamide products interchangeability. Glibenclamide pharmacokinetics is characterised by high interindividual variability. This may lead to both an increased risk of hypoglycemia and drug inefficacy, therefore, when prescribing glibenclamide, a physician should carefully control the efficacy and safety of drug therapy.

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period.

By the middle of 2021, the official global number of coronavirus disease 2019 (COVID-19) patients was close to 230 million, but the number accounting for asymptomatic patients was much higher. Consequences and rehabilitation after COVID-19 are of particular interest and raise many controversial and unresolved issues. On May 18, 2021, the Eurasian Association of Therapists organized an international panel of experts to analyze challenges associated with the post-COVID-19 period. This panel aimed to develop approaches to identify gaps in the discussed issues. This interdisciplinary team of leading experts reviewed the current literature and presented their data to formulate practical guidance on management of patients after COVID-19. The panel of experts also presented recommendations on how to implement the gained knowledge into health care practices.

The international AKTIV register presents a detailed description of out- and inpatients with COVID-19 in the Eurasian region. It was found that hospitalized patients had more comorbidities. In addition, these patients were older and there were more men than among outpatients. Among the traditional risk factors, obesity and hypertension had a significant negative effect on prognosis, which was more significant for patients 60 years of age and older. Among comorbidities, CVDs had the maximum negative effect on prognosis, and this effect was more significant for patients 60 years of age and older. Among other comorbidities, type 2 and 1 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer and anemia had a negative impact on the prognosis. This effect was also more significant (with the exception of type 1 diabetes) for patients 60 years and older. The death risk in patients with COVID-19 depended on the severity and type of multimorbidity. Clusters of diseases typical for deceased patients were identified and their impact on prognosis was determined. The most unfavorable was a cluster of 4 diseases, including hypertension, coronary artery disease, heart failure, and diabetes mellitus. The data obtained should be taken into account when planning measures for prevention (vaccination priority groups), treatment and rehabilitation of COVID-19 survivors.

The organizer of the registers “Dynamics analysis of comorbidities in SARSCoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients.

Introduction. Busereline, being a synthetic gonadotropin-releasing hormone analog, is widely used for hormone-dependent cancer treatment (e.g. prostate cancer and breast cancer). Based on the accumulated scientific data for busereline quantitation in biosamples, the main analytical method that is used for this purpose is high-performance liquid chromatography (HPLC) with fluorescence detection, combined with protein precipitation (TCA 10%) for sample preparation. However, due to several limitations of this method resulting in low sensitivity (at the µg/mL level of concentrations), the HPLC-MS/MS analytical method was chosen for peptide determination in biosamples. The HPLC-MS/MS method is considered to have higher accuracy and specificity. The main sample preparation method for gonadotropin-releasing hormone analogs is solid-phase extraction. In our work, we’ve chosen protein precipitation as an alternative – easier and less laborious biosamples preparation process.Aim. The main objective of this study was the development and validation of HPLC-MS/MS method for busereline quantitation in animal (mini pigs) plasma samples and its further application to pharmacokinetic studies.Materials and methods. Busereline quantitative determination in plasma samples was performed using HPLC-MS/MS method. A protein precipitation procedure (methanol, 1:2, v/v) was used for busereline extraction from pig plasma.Results and discussion. The developed analytical method was validated for selectivity, linearity, matrix effect, accuracy (intra-day, inter-day), precision (intra-day, inter-day), LLOQ, carryover and stability.Conclusion. A new HPLC-MS/MS method for busereline quantitation in blood plasma was developed and successfully validated. The developed method showed linearity over the quantitation range from 1 to 20 ng/mL. The developed method can be successfully applied to busereline pharmacokinetic studies.

Introduction. Tadalafil is a drug used to treat erectile dysfunction. For the quantitative determination of tadalafil in human plasma are used methods of high performance liquid chromatography with ultraviolet and tandem mass spectrometric detection, during the analytical part of pharmacokinetic studies. In the majority of the considered methods the method of liquid-liquid extraction and the method of solid-phase extraction are used, these methods are difficult and expensive. Therefore, the method of protein precipitation was considered as sample preparation. This method is simple and there is important to analysis a lot of clinical samples in bioequivalence studies.Aim. The aim of this study is to develop method for the quantitative determination of tadalafil in human plasma by HPLC-MS for the analytical part of pharmacokinetic studies.Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-MS. A sample was prepared using acetonitrile protein precipitation.Results and discussion. This method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability.Conclusion. The method of the quantitative determination of tadalafil in human plasma was developed and validated by HPLC-MS. The analytical range of the was 5,00–1000,00 ng/ml tadalafil in plasma. Method could be applied to determination of tadalafil in plasma for PK and BE studies.

Introduction. Coenzyme Q10 plays an important role in the human body. Its main function is not only the transfer of electrons in the mitochondrial respiratory chain for the ATP synthesis, but it is also one of the most powerful antioxidants in the body.The aim of research is to monitor the relationship between cardiovascular and pulmonary diseases, and the concentration of coenzyme Q10 in the blood plasma.Materials and methods. Coenzyme Q10 was determined using high performance liquid chromatography with mass spectrometric detection.Results and discussion. During the study, it was found that the concentration of coenzyme Q10 in plasma is affected not only by the main diseases, but also by comorbidities, as well as by the therapy. A sharp decrease in plasma coenzyme Q10 concentration was noted in patients with cardiovascular pathologies, especially in those with concomitant endocrine diseases. Also, it was recorded a decrease in the concentration of coenzyme Q10 in the plasma of patients with pneumonia. Conclusion. During the experiment, the coenzyme Q10 concentration was found to be dependent on cardiovascular and pulmonary diseases.

Background. The relative availability of Phenazepam makes it a frequent cause of overdose, suicide and non-medical use. At the same time, it remains insufficiently studied in chemical and toxicological terms.The aim of study. to create an accessible, rapid method for detecting Phenazepam in biological matrices of patients with acute poisoning.Materials and methods. We used thin-layer chromatography (TLC), gas chromatography with a mass selective detector (GC-MS), high performance liquid chromatography with a tandem mass-selective detector (LC-MS/MS) and immunochromatographic analysis (ICA). The preparation of samples of intact urine with the addition of standard solutions of Phenazepam and real urine samples of patients with acute poisoning with Phenazepam was carried out using liquid-liquid extraction or precipitation of related components of the sample with acetonitrile. Hydrolysis and derivatization were also added in GC-MS analysis.Results. The analysis of statistics of the Department of Acute Poisonings of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2014-2016 showed that Phenazepam poisonings averaged 9.2% of the total number of admissions and mainly occurred as suicidal attempts. A technique has been developed for the detection of Phenazepam by TLC, which gives more objective results than ICA. For confirmatory analysis, it is advisable to use LC-MS/MS method for the native substance and GC-MS for the products of hydrolysis after derivatization. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment, difficult sample preparation, and makes it possible to reliably detect toxic and lethal concentrations of Phenazepam.

A method for quantification of capecitabine and 5-fluorouracil in human plasma was developed. The sample preparation was carried out by protein precipitation with methanol. The quantitative determination was performed by HPLC with a triple quadrupole mass-detector. The method was validated in terms of selectivity, calibration curve, accuracy, precision, lower limit of quantification, and stability. The analytical range was 10.0-20000.0 ng/mL for capecitabine and 10.0-400.0 ng/ml for 5-fluorouracil. The developed method may be used for bioequivalence studies of capecitabine drug products.

The express method for simultaneous determination of enalapril and enalaprilat in human serum using HPLC-MS/MS is proposed. A simple sample preparation procedure, short analysis time, and a wide analytical range for both analytes (5.00 to 250.00 ng/mL) characterize this method. This technique is useful for carrying out routine research, such as therapeutic drug monitoring, bioequivalence studies and evaluation of the interchangeability of enalapril drug products.

A new method for determination of moxifloxacin in human plasma using HPLC with UV-detection is described. The sample preparation was made by protein precipitation by 50% trifluoracetic acid solution. The method was validated in terms of selectivity, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability. The analytical range was 100-5000 ng/mL. Limit of determination was 31 ng/mL. Method could be applied to moxifloxacin determination in plasma for PK and BE studies.

COVID-19 is a severe infection with high mortality. The concept of the disease has been shaped to a greater extent on the basis of large registers from the USA, Spain, Italy, and China. However, there is no information on the disease characteristics in Caucasian patients.Therefore, we created an international register with the estimated capacity of 5,000 patients — Dynamics Analysis of Comorbidities in SARS-CoV-2 Survivors (AKTIV SARS-CoV-2), which brought together professionals from the Russian Federation, Republic of Armenia, Republic of Kazakhstan, and Kyrgyz Republic. The article presents the first analysis of the register involving 1,003 patients. It was shown that the most significant difference of the Caucasian population was the higher effect of multimorbidity on the mortality risk vs other registers. More pronounced effect on mortality of such diseases as diabetes, obesity, hypertension, chronic kidney disease, and age over 60 years was also revealed.

Carbamazepine is the drug of first choice in the treatment of trigeminal neuralgia, epilepsy and other neurological diseases. Carbamazepine is known to have a narrow therapeutic range, and hereby the auto-induction of its metabolism with prolonged use cause the reduction of its therapeutic efficacy. Phenotyping of patients by the rate of carbamazepine metabolism allows to perform individual drug dose adjustment and to avoid the occurrence of adverse drug effects. In order to implement the mentioned approach, the method for simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in human serum using HPLC-MS/MS was developed.

Single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene were found by sequencing the clinical exome of a group of men who died of sudden cardiac death (SCD) at the age of 45 years. The aim of the study is to study the association of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD in a case-control study using routine molecular genetic analysis. Material and methods. SCD group (n = 400, mean age 53.2 ± 8.7 years, 70.9 % men, 29.1 % women) was formed using the SCD criteria of the European Society of Cardiology from the anonymous DNA bank of the deceased sudden death (1999–2019). The control group (n = 400, mean age 53.1 ± 8.3 years, 68.3 % men, 31.7 % women) was matched by sex and age to the SCD group from DNA banks of international projects MONICA and HAPIEE of living at the time of researches participants. Genotyping was carried out using the polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. There were no statistically significant differences in the frequencies of genotypes and alleles of single nucleotide polymorphisms rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene between the SCD group and the control group (p > 0.05). Conclusions. The association of single nucleotide rs1008832 of the CACNA1C gene, rs4027402 of the SYNE2 gene, rs2340917 of the TMEM43 gene, rs58225473 of the CACNB2 gene with SCD has not been confirmed.