Статья получена: 15.01.2020. Статья принята к печати: 21.02.2020 Резюме Введение. ВИЧ-инфекция является одним из наиболее актуальных заболеваний современности с медицинской, эпидемиологической и социальной точки зрения. Своевременная диагностика, выявление и контроль заболевания, адекватное назначение антиретровирусной терапии позволяют в достаточной степени снизить вирусную нагрузку на организм пациента, снизить риски передачи инфекции. В настоящее время в качестве терапии всё чаще назначаются комбинации различных антиретровирусных лекарственных средств. Одной из перспективных комбинаций является совместное применение атазанавира и ритонавира. Важнейшим этапом для изучения фармакокинетического взаимодействия, исследований сравнительной фармакокинетики и биоэквивалентности является разработка аналитической методики, позволяющей определять исследуемые вещества в плазме крови человека. В настоящее время нет опубликованных методик о совместном определении атазанавира и ритонавира в плазме крови человека с помощью метода высокоэффективной жидкостной хроматографии с массселективным детектированием с применением одноквадрупольного масс-детектора. В данной работе приведена разработка и валидация методики совместного определения атазанавира и ритонавира в плазме крови после пробоподготовки способом осаждения белков. Цель. Целью исследования является разработка методики количественного определения атазанавира и ритонавира в плазме крови человека методом высокоэффективной жидкостной хроматографии с одноквадрупольным масс-спектрометрическим детектированием (ВЭЖХ-МС) для проведения аналитической части фармакокинетических исследований. Материалы и методы. Количественное определение атазанавира и ритонавира в плазме крови человека методом ВЭЖХ-МС. В качестве пробоподготовки был использован способ осаждения белков. Результаты и обсуждение. Разработанная методика была валидирована по следующим валидационным параметрам: селективность, эффект матрицы, линейность, точность, прецизионность, предел количественного определения, перенос пробы, стабильность. Заключение. Разработана и валидирована методика количественного определения атазанавира и ритонавира в плазме крови человека методом ВЭЖХ-МС. Подтвержденный аналитический диапазон методики составил 50,0-10000,0 нг/мл для атазанавира и 10,0-2500,0 нг/мл для ритонавира. Полученный аналитический диапазон позволяет применять разработанную методику для проведения аналитической части исследований фармакокинетики препаратов, содержащих атазанавир и ритонавир.

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. Multicomponent oral drugs containing salbutamol, bromhexine, ambroxol and guaifenesin have a mucolytic, expectorant and bronchodilator effect. The development method for determination substances in biological fluids is a main procedure for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs. There is no published data of the determination of bromhexine, ambroxol and guaifenesin, but there a lot of published methods for divided determination analytes in a biological fluid. This study presents the development and validation of a method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human blood plasma by high performance liquid chromatography with tandem mass spectrometric detection. A sample preparation was perfomed by solid-phase extraction. Deuterated derivatives were used as internal standards.Aim. The aim of the study is to develop a method for the quantitative determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection. A sample was prepared using solid-phase extraction.Results and discussion. The method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over and stability.Conclusion. The method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma was developed and validated by HPLC-MS/MS. The analytical range of the was 0.1–20 ng/mL in plasma for salbutamol, 0.25–25 ng/mL in plasma for bromhexine, 0.075–3 ng/mL in plasma for ambroxol, and 10–2000 ng/mL in plasma for guaifenesin. Method could be applied to determination of salbutamol, bromhexine, ambroxol and guaifenesin in plasma for PK and BE studies.

Introduction. Viral infections are a serious problem that occurs during the use of immunosuppressants in preparation for organ transplantation and in the postoperative period. Cytomegalovirus (CMV) infection is one of the main causes of diseases in people with weakened immune systems. It has a direct impact on one’s body and makes it more likely to reject a transplanted organ. Antiviral drugs are used to treat and prevent this infectious disease. Valganciclovir is a prodrug whose active metabolite is ganciclovir. Valganciclovir is the drug of choice in the treatment of CMV infections. Currently, there are no researches on the matter of simultaneous determination of both valganciclovir and ganciclovir in human blood plasma by means of high-performance liquid chromatography (HPLC) with ultraviolet detection. This research delivers a thorough description of development and validation of a particular method for simultaneous determination of valganciclovir and ganciclovir in the plasma after sample preparation by the method of protein precipitation.Aim. The aim of this study is to develop method for the quantitative determination of valganciclovir and its active metabolite ganciclovir in human plasma by HPLC-UV for pharmacokinetic studies.Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-UV. A sample was prepared using 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 valganciclovir and its active metabolite ganciclovir in human plasma was developed and validated by HPLC-UV. The analytical range of the was 5,0–1000,0 ng/ml for valganciclovir and 100,0–10000,0 ng/ml for ganciclovir in plasma. Method could be applied to determination of valganciclovir and ganciclovir in plasma for PK and BE studies.

Introduction. Human Immunodeficiency Virus (HIV) is one of the main socially significant infection all over the world. HIV-positive patients take medical care, including antiretroviral drugs (ARVs) pharmacotherapy. Like all drugs, ARVs have lots of side effects that should be taken when prescribing drugs as part of highly active antiretroviral therapy. There are many cases when side effects of ARVs caused patients to enter the toxicology department. Therefore, the development of new methods for the analysis of ARV in biological fluids for the timely diagnosis of treatment of poisoning of this group of drugs is relevant today.Aim. The aim of this study is development of screening analysis of atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in the urine to identify these drugs as possible toxicants for poisoning by high-performance liquid chromatography with tandem massselective detection (HPLC-MS/MS).Materials and methods. Identification of ARV was performed by HPLC-MS/MS. Methanol precipitation method was used as a sample preparation.Results and discussion. The optimal conditions for sample preparation, chromatographic separation, and mass-spectrometric detection were selected to determine the studied ARVs. This method was tested on urine samples from patients in the Department of Acute Poisoning and Somatopsychiatric Disorders (OOSPD) with acute ARV poisoning.Conclusion. This screening method for analyse atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in human urine has been developed by HPLC-MS/MS. The developed method can be used to identify these drugs as possible toxicants in case of poisoning. The prospect for the development of the topic is the inclusion of new molecules in the method and quantitative determination of the studied ARVs.