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Aim. Development of methods for the determination of felodipine in blood and plasma. Methods. The study object was felodipine [3-ethyl-5-methyl-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate]. The experiments were carried out on model mixtures of felodipine with blood and human blood plasma. Acetone was proposed as an isolating agent for the extraction of felodipine from biological fluids. To identify and quantify felodipine in extracts from blood and plasma, the methods of thin-layer chromatography, spectrophotometry and gas-liquid chromatography in combination with mass spectrometry were proposed. Results. The possibility of using acetone as an isolating agent to extract felodipine from biological fluids is demonstrated. The optimal conditions for the extraction of felodipine with acetone were found to be achieved already at 2-fold infusion of a biological object with an isolating agent, if the mass ratio of isolating liquid and biological material at each infusion stage is at least 2:1, and the infusion time is at least 30 minutes. Optimal felodipine purification conditions were achieved in a macrocolumn (15×1 cm) of Silasorb S-18 sorbent of 30 μm with elution of the substance with the polar eluent acetonitrile-water (7:3). The methods of determining felodipine in the blood and plasma were developed. With the content of felodipine of 25 mg in 25 g of biological fluid, the developed methods allow determining 86.01–87.86% in blood and 95.64–96.18% of the substance in blood plasma. The values of the detection limit of felodipine in the blood and plasma by the developed methods are 200 μg/100 g and 150 μg/100 g, respectively. Conclusion. Methods for the determination of felodipine in biological fluids were developed based on isolating with acetone and purification in the Silasorb S-18 sorbent column; use of these methods allows determining up to 87.86% of the analyte in the blood and up to 96.18% in the blood plasma.

Forensic chemical examination is carried out in order to isolate, identify and quantify toxic, narcotic, psychotropic and potent substances in the organs and fluids of the human body. The present study we researched the process of extraction of 2,3-benzodiazepine - tofisopam. There have been cases of tofisopam poisoning. And there are no descriptions of tofisopam isolation from biological fluids in the literature. Liquid extraction, an effective and commonly used method of isolation in the chemical-toxicological analysis, is used when extracting substances from blood, lymph, saliva, urine and stomach washings. The process of isolation may be influenced by the nature of the organic solvent, pH, the presence of an electrolyte, time and frequency of extraction. We have studied the effect of each factor on tofisopam isolation from aqueous solutions. It has been found that the optimal organic solvent for the extraction of the solutions is dichloroethane, which extracts maximum amount of the analyte at pH = 5.0. Saturated sodium sulphate has a salting-in effect for tofisopam. The optimum conditions for tofisopam isolating are 7 minutes with double extraction. Based on the research method of tofisopam isolating the model mixture of urine was developed. We found that this model urine mixture isolates 66.51-67.9l % of tofisopam. We performed validation assessment of the developed method for evaluation of precision and accuracy. The assessment showed the suitability of techniques for the analysis.

Based on the measured IR and H1NMR spectra of the substance 4-amino-3-(3-pyridyl)-butanoic acid dihydrochlorid carried interpretation of absorption and structural fragments installed analyte. The results led to the recommendation of these research methods to be used in pharmaceutical analysis as a substance and a drug for structure determination and identification of the substance.

Цель. Для изучения биоэквивалентности таблетированной формы силденафила (таблетки «Тегрум» 100 мг), производства ООО «НПФ «Микрохим» (г. Рубежное, Украина) был разработан и валидирован быстрый, простой и специфический метод количественного определения концентрации силденафила и его активного метаболита - N-десметил силденафила в плазме крови человека с применением внутренних стандартов, меченных атомами дейтерия. Извлечение аналитов из плазмы крови выполнялось методом прямой жидкость-жидкостной экстракции.Методы. Содержание силденафила и его десметилированного метаболита определяли в надосадочной жидкости методом высокоэффективной жидкостной хроматографии с тандемным масс-спектрометрическим детектированием. Ионизацию cилденафила, N-десметил силденафила, cилденафила-d8 и N-десметил силденафила-d8 проводили электрораспылением в положительном режиме (ESI, Positive). При детектировании использовали мониторинг мультиреакций (MRM) выбранных материнских ионов с m/z 475,30; 483,20; 461,20; 469,20. Дочерний ион был выбран с m/z 283,10 для всех анализируемых соединений.Результаты. В ходе валидации данного метода в линейном диапазоне 5,05-1009,92 нг/мл для силденафила и 2,24-400,84 нг/мл для N-десметил силденафила коэффициент корреляции (r2) составил 0,9975 и 0,9973 соответственно, также была продемонстрирована надёжная правильность и воспроизводимость результатов для обеих аналитов.Выводы. Разработан и валидирован простой, специфический и чувствительный ВЭЖХ-МС/МС метод количественного определения концентрации силденафила и его активного метаболита N-десметил силденафила в плазме крови человека с применением меченных стабильными изотопами внутренних стандартов - силденафил-d8 и N-десметил силденафил- d8. Разработанный нами экспресс-метод подготовки биологических образцов, позволяет исключить влияние биологической матрицы на получаемые результаты и определять низкие концентрации обоих аналитов в надосадочной жидкости без применения таких трудоемких и времязатратных процедур, как концентрирование пробы, восстановление сухого остатка или дорогостоящей твердофазной экстракции. Экспериментальные данные, полученные в ходе полной валидации метода, соответствуют установленным национальным и международным требованиям, а так же подтверждают высокую специфичность, чувствительность, точность, воспроизводимость и экономичность разработанного нами метода., Aim. To assess bioequivalence of sildenafil citrate tablet formulation produced by pharmaceutical company “Microkhim” (Rubezhnoe, Ukraine) it was developed and validated a prompt, specific and quite simple method for quantitative determination of sildenafil and its active metabolite - N-desmethyl sildenafil concentrations in the human blood using deuterium labeled internal standards. Direct liquid-liquid extraction procedure was utilized to extract the analytes from the blood plasma.Methods. Contents of sildenafil and its metabolite in supernatant were determined by means of the high performance liquid chromatography / tandem mass spectrometric detection technique. Ionization of sildenafil, N-desmethyl sildenafil, sildenafil-d8 and N-desmethyl sildenafil-d8 was performed in the positive electrospray mode (ESI, Positive). Detection of the analytes was carried out in the multi reactions monitoring (MRM) regimen with the following m/z values for selected parent ions: 475,30; 483,20; 461,20 and 469,20, respectively. The daughter ion m/z value was selected to be 283,10 for all analytes.Results. Analytical method proposed proved to demonstrate reliable accuracy and reproducibility for both analytes and has been validated within linear range 5,05-1009,92 ng/ml for sildenafil and 2,24-400,84 ng/mL for N-desmethyl sildenafil with correlation coefficient (r2) equaled to 0.9975 and 0.9973, respectively.Conclusions. It was developed and validated a simple, specific and sensitive HPLC-MS/MS method for quantitative determination of sildenafil and its active metabolite N-desmethyl sildenafil concentrations in human blood plasma utilizing stable isotope labeled internal standards – deuterated sildenafil-d8 and N-desmethyl sildenafil- d8. Important feature of the method was a modified preanalytical procedures of biological samples preparation – direct liquid-liquid extraction that allowed to avoid laborious and time-consuming procedures such as evaporation to concentrate the samples with consequent recovery of dry residue, as well as to refuse from expensive solid-phase extraction. Application of the deuterium labeled internal standards allowed to suppress a biological matrix effect drastically, as well as to reach target LLOQ level. Experimental data obtained in the course of full validation of the method proposed that was performed in accordance with approved national and international technical and regulatory requirements, allowed to affirm high specificity, sensitivity, accuracy, reproducibility and efficiency of the method.

Biosensors are chemical sensors that take advantage of the high selectivity and sensitivity of a biologically active material. In this work, biosensor applications of the piezoelectric quartz sensor are reviewed. Among all physical transducers, piezoelectric systems have emerged as the most attractive due to their simplicity, low instrumentation costs, possibility for real-time and label-free detection and generally high sensitivity, Биосенсоры ‑ это химические датчики, которые используют в своих интересах высокую селективность и чувствительность биологически активного материала. В этой работе рассмотрены возможные применения пьезоэлектрического кварцевого сенсора. Среди всех физических преобразователей, пьезоэлектрические системы являются наиболее привлекательными благодаря своей простоте, низкой себестоимости изготавливаемых приборов, возможности работы в реальном масштабе времени и, как правило, низкой себестоимости