Development of Genistein Synthesis for Use as a Certified Reference Material

Introduction. The use of certified reference materials (CRMs) ensures metrological traceability and comparability of analysis results performed in different laboratories, by different analysts, at different times. Genistein is a promising substance with a wide spectrum of pharmacological action. genistein is widely used in dietary supplements. Development of regulatory documents for CRM of genistein will ensure the quality of drugs and dietary supplements.Aim. Aim of our study is to improve of the ways of synthesis and determination of spectrum characteristics of genistein for the certification of CRM.Materials and methods. We used synthetic genistein, (Ph.D. V. Yu. Kovtun SPC "Pharmzashchita") (sample № 1) and genistein synthesized and studied at the departments of pharmaceutical chemistry and chemical technology of medicinal substances SPCPU (sample № 2). Infrared spectra of genistein samples were collected on an FSM 1201 infrared Fourier spectrometer (OOO Infraspek, Russia) via KBr pellets technique. All the spectra were collected in the 4000–500 cm−1 range. The NMR (1H and 13C) measurements were performed with a BrukerAvance III NMR spectrometer (400 and 100 MHz) (Bruker, Germany) in DMSO-d6 solvent. Raman spectra were recorded by an ORTES-785TRS-2700 analytical Raman scattering system at a laser power of 100 mW (OPTEC JSC, Russia). Laser interaction time was 5, 10, 20 and 60 seconds. The results were processed using the software "BWSpec 4.10_4", USA. GC-MS was performed on an Agilent Technologies 7890A gas chromatograph (Agilent Technologies, USA) with a 7693 autoinjector and a Hewlett Packard 5975C mass selective detector.Results and discussion. The synthesis was carried out according to the developer's method. The stage "removal of the alkyl protection" has been improved. The spectra of the synthesis intermediate of genistein (biochanin A) correspond to the literature data. Samples of genistein were investigated by methods: MC and NMR 13С, 1Н. The structure of the investigated substance was confirmed; Raman and IR spectroscopy showed that the spectra of the samples do not differ from each other and there are no additional signals.Conclusion. The spectrum characteristics of samples of genistein were obtained by NMR, IR and Raman spectroscopy, which will be used in the regulatory documentation for CRM of genistein. All of this will make it possible to control the quality of medicines based on it and to identify substandard dietary supplements.

Deep learning reveals personalized spatial spectral abnormalities of high delta and low alpha bands in EEG of patients with early Parkinson’s disease

Objective. Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and early diagnosis is crucial to delay disease progression. The diagnosis of early PD has always been a difficult clinical problem due to the lack of reliable biomarkers. Electroencephalogram (EEG) is the most common clinical detection method, and studies have attempted to discover the EEG spectrum characteristics of early PD, but the reported conclusions are not uniform due to the heterogeneity of early PD patients. There is an urgent need for a more advanced algorithm to extract spectrum characteristics from EEG to satisfy the personalized requirements. Approach. The structured power spectral density with spatial distribution was used as the input of convolutional neural network (CNN). A visualization technique called gradient-weighted class activation mapping (Grad-CAM) was used to extract the optimal frequency bands for identifying early PD. Based on the model visualization, we proposed a novel quantitative index of spectral characteristics, spatial-mapping relative power (SRP), to detect personalized abnormalities in the spatial spectral characteristics of EEG in early PD. Main results. We demonstrated the feasibility of applying CNN to identify the patients with early PD with an accuracy of 99.87% ± 0.03%. The models indicated the characteristic frequency bands (high-delta (3.5-4.5 Hz) and low-alpha (7.5-11 Hz) frequency bands) that are used to identify the early PD. The SRP of these two characteristic bands in early PD patients was significantly higher than that in the control group, and the abnormalities were consistent at the group and individual levels. Significance. This study provides a novel personalized detection algorithm based on deep learning to reveal the optimal frequency bands for identifying early PD and obtain the spatial frequency characteristics of early PD. The findings of this study will provide an effective reference for the auxiliary diagnosis of early PD in clinical practice.

Control of spectral characteristics of the medical accelerator on the basis of comparison of mass weaking coefficients of different materials

Background. Radiation protection of patients undergoing radiation therapy using linear electron accelerators is based on ensuring the constancy of the equipment parameters set during commissioning. Therefore, studying the possibility of operational assessment of the spectrum characteristics consistency of the generated bremsstrahlung is a priority along with standard dosimetric parameter control procedures. Primarily, this refers to specifying the average measured energy of bremsstrahlung which provides an impartial assessment of the constancy of the whole wave path of the accelerator. However, there is no special diagnostic equipment to determine this parameter. At the same time, the literature data represent a growing interest in the use of CdTe sensors for the analysis of high-energy radiation, including the ones in medical accelerators. Purpose – developing and testing special diagnostic equipment based on semiconductor CdTe sensors, which would implement the assessment of the average measured energy of bremsstrahlung of the medical accelerator 6 MeV via comparing the mass attenuation coefficients in lead and aluminum. Materials and Methods. The paper deals with experimental evaluation of the Varian Clinac 600C linear accelerator (USA) spectrum characteristics carried out at Radiation Oncology Department of State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine» via determining the average measured energy of bremsstrahlung. The assessment of the average measured energy of the bremsstrahlung of the accelerator was performed based on comparing two mass attenuation coefficients of radiation with materials having significantly different atomic numbers, i.e. Al and Pb. The assessment of the mass attenuation coefficients was performed on the basis of measuring the average amplitudes of CdTe signals of the sensor, operating in the pulse mode in conjunction with a 16-bit ADC. Pulses of bremsstrahlung from the linear accelerator were recorded by a peak detector for 10 seconds of measurement by the hardware-software complex at 400 monitor units by CdTe sensor with aluminum and lead absorber. The study was performed at a distance of «source-surface» 100 cm with an area of the irradiation field of 20x20 cm. The spectral energy profile of the generated field of bremsstrahlung was studied. Results. The developed equipment was tested by CdTe sensor, which was created taking into account the energy sensitivity of the sensor itself as well as the spectraltemporal characteristics of the pulsed radiation of the accelerator. The approach dealing with assessing the average measured energy of bremsstrahlung of the linear electron accelerator, based on the dependence of the attenuation of radiation by the absorber layer on the radiation energy, has been experimentally confirmed. The theoretical dependence of the average measured energy of bremsstrahlung of the linear accelerator on the ratio of the mass attenuation coefficients of lead and aluminum has been obtained. The energy range from 0.1 to 6 MeV corresponds to the ratio of mass absorption coefficients of lead to aluminum, varying nonlinearly from 33.8 to 1.639. The average measured energy of the linear accelerator of 0.8 MeV corresponds to a mass coefficient ratio of about 1.23 for these materials. The assessed absolute error (from the set value during commissioning the linear accelerator) of the specified measured average energy of bremsstrahlung is up to 12.5% (0.72 MeV), corresponding to the ratio of mass attenuation coefficients – 1.340. Conclusions. The special diagnostic equipment for recording the spectrum characteristics of the Varian Clinac 600C linear accelerator (USA) based on semiconductor CdTe sensors, which along with 16-bit ADC make it possible to estimate the average measured energy of bremsstrahlung via comparing mass attenuation coefficients in Al and Pb has been substantiated and reduced to practice. The assessment of mass attenuation coefficients is carried out based on measuring the average amplitudes of pulses of СdTe sensors operating in a pulse mode.