RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).
Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/administração & dosagem , Alanina/administração & dosagem , COVID-19/epidemiologia , China/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/efeitos dos fármacosRESUMO
Five 2C-series of phenethylamine designer drugs, including 2,5-dimethoxy-4-ethylthio-phenethylamine (2C-T-2), 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), 4-chloro-2,5-dimethoxyphenethylamine (2C-C), 4-bromo-2,5-dimethoxy-phenethylamine (2C-B), 2,5-dimethoxy-4-iodo-phenethylamine (2C-I), were synthesized and standard GC/MS and fluorescence spectra are reported for them. A mixture of the five drugs was separated and detected by means of capillary electrophoresis (CE) with native fluorescence and light emitting diode (LED)-induced fluorescence (LIF) detection, respectively, for comparison. In the former case, exciting at a wavelength of 300 nm from a Xe lamp was used. The detection limits were found to be only in the range of approximately 10(-4) M by the micellar electrokinetic chromatography (MEKC) mode but were improved to approximately 10(-7) M when the sweeping-MEKC mode was used. For a highly sensitive analysis, LED-induced fluorescence detection was examined by derivatizing the compounds with a fluorescent dye, fluorescein isothiocyanate isomer I (FITC). A blue-LED (approximately 2 mW) was used as the fluorescence excitation source. The detection limits were improved to approximately 10(-7) and approximately 10(-8) M, respectively, when the MEKC and stacking-MEKC modes were applied. A mimic urine sample was obtained by spiking urine from a volunteer with the five standards, and after liquid-liquid extraction, the sample was examined by means of the MEKC-LIF mode. The extraction procedures used for the urine sample and the CE conditions for the separation were optimized.
Assuntos
Eletroforese Capilar/métodos , Fenetilaminas/isolamento & purificação , Cromatografia Capilar Eletrocinética Micelar/métodos , Drogas Desenhadas/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fenetilaminas/urina , Espectrometria de FluorescênciaRESUMO
In sample-stacking techniques, the detection limit cannot be improved by simply increasing the length of the sample solution, because the individual electrophoretic parameters must be optimized. In an attempt to increase the amount of sample injected, as well as to focus them onto a small zone, two novel methods are proposed. One of these employs an "ultra-high conductivity zone", which was inserted between the sample zone and background solution to build an unequal conductivity gradient. The other employs a "low temperature bath". A portion of the capillary (near the junction between the sample solution and the background solution) was immersed in a low temperature bath, which served as a "pseudo-high-conductivity zone" due to the fact that conductivity would increases when the temperature is decreased. As a result, a large volume of sample injection can be achieved. Using 3,4-methylenedioxymethamphetamine as a model compound, the detection limit was determined to be 1.6 x 10(-6) M (S/N = 3) by means of normal non-aqueous capillary electrophoresis (NACE). This could be improved to 3.0 x 10(-8) M, 4.8 x 10(-9) M and 5.0 x 10(-9) M, respectively, when the normal stacking, ultra-high conductivity zone NACE-stacking and the low-temperature zone NACE-stacking methods were applied.
Assuntos
Eletroforese Capilar/métodos , Indicadores e Reagentes , N-Metil-3,4-Metilenodioxianfetamina/análise , Solventes/químicaRESUMO
The chiral separation of (+/-)-methamphetamine, (+/-)-methcathinone, (+/-)-ephedrine and (+/-)-pseudoephedrine by means of beta-cyclodextrine modified capillary electrophoresis is described. The distribution of enantiomers in clandestine tablets and urine samples were identified. Several electrophoretic parameters such as the concentration of beta-cyclodextrin, temperature, the applied voltage and the amount of organic solvent required for successful separation were optimized. The method, as described herein, represents a good complementary method to GC-MS for use in forensic and clinical analysis.
Assuntos
Ciclodextrinas , Eletroforese Capilar/métodos , Medicina Legal/métodos , Drogas Ilícitas/química , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Estimulantes do Sistema Nervoso Central/urina , Efedrina/química , Efedrina/isolamento & purificação , Efedrina/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metanfetamina/química , Metanfetamina/isolamento & purificação , Metanfetamina/urina , Estrutura Molecular , Propiofenonas/química , Propiofenonas/isolamento & purificação , Propiofenonas/urina , Estereoisomerismo , ComprimidosRESUMO
A comparison of the use of aqueous and nonaqueous buffers in association with beta-CD for the chiral separation of (R)- and (S)-3,4-methylenedioxymethamphetamine and related compounds is described. The (R)- and (S)-isomers of 3,4-methylenedioxymethamphetamine (MDMA) and its major metabolite 3,4-methylenedioxyamphetamine (MDA) were prepared. Under aqueous and nonaqueous buffer conditions and based on the CZE and MEKC modes, the order of migration of (R)-MDA, (S)-MDA, (R)-MDMA, and the (S)-MDMA enantioisomers were determined. Several electrophoretic parameters, including the concentration of beta-CD (aqueous, 25-60 mM; nonaqueous, 20-150 mM) used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized.