RESUMEN
OBJECTIVES: In the present study, an eco- friendly micellar liquid chromatographic technique was validated for separation and quantification of two drugs; namely ribavirin (RIV), and sofosbuvir (SBV) in pure form, pharmaceuticals containing them, human plasma and human urine. These drugs are administered co-administered for treatment of Hepatitis C virus (HCV) that causes hepatitis C in humans. MATERIAL AND METHODS: These drugs were separated using Nucleosil 100-5 phenyl column. Sodium dodecyl sulphate (SDS) solution (0.05M, pH 7.0) containing triethylamine (0.3%) and n-butanol (10%) was used as a mobile phase with 1.2 mLmin-1 ï¬ow rate and 215nm detection wavelength. Nine minutes were required for resolving the two drugs from the matrix. RESULTS: The method showed good linearity for RIV and SBV with correlation coefficients (r2) more than 0.9996 within the concentration ranges of (20-400) and (40-400) ngmL-1 in pure form, (30-300) and (50-300) ngmL-1 in human plasma and (20-400) and (40-400) ngmL-1 in human urine, respectively. CONCLUSION: The recommended method was applied for examination of RIV and SBV in pure and pharmaceuticals. The obtained results were statistically matched with reported methods with no significant differences. Also, the recommended method was effectively applied for estimation of both drugs in spiked human urine and plasma without purification or extraction steps and real samples of plasma and urine of humans having therapy of RIV and SBV, as well as, performing tablets dissolution-rate tests with satisfactory results.
Asunto(s)
Antivirales/análisis , Hepatitis C/tratamiento farmacológico , Antivirales/sangre , Antivirales/orina , Cromatografía Líquida de Alta Presión/métodos , Análisis Costo-Beneficio , Humanos , Límite de Detección , Reproducibilidad de los Resultados , Ribavirina/análisis , Ribavirina/sangre , Ribavirina/orina , Sofosbuvir/análisis , Sofosbuvir/sangre , Sofosbuvir/orina , SolubilidadRESUMEN
Sofosbuvir is an NS5B nucleotide inhibitor for the treatment of hepatitis C viral infection. In this study the pharmacokinetics (PK) and safety of single and multiple doses of generic sofosbuvir were investigated in healthy Chinese subjects. Twelve subjects (6 male and 6 female) were enrolled in this study. The PK parameters of sofosbuvir and its metabolite (GS-331007) in both blood and urine samples were analyzed after dosing by the established liquid chromatography tandem mass spectrometry analytical method. The safety/tolerability assessment consisted of documenting adverse events, vital signs, electrocardiogram, and laboratory test results. Sofosbuvir was well tolerated. Major PK parameters of the generic formulation of sofosbuvir were similar to those found in previous reports. These data support further clinical evaluation of this generic formulation of sofosbuvir.
Asunto(s)
Antivirales/farmacocinética , Medicamentos Genéricos/farmacocinética , Sofosbuvir/farmacocinética , Uridina/análogos & derivados , Administración Oral , Adulto , Antivirales/efectos adversos , Antivirales/sangre , Antivirales/orina , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Medicamentos Genéricos/efectos adversos , Femenino , Voluntarios Sanos , Hepacivirus/efectos de los fármacos , Humanos , Masculino , Tasa de Depuración Metabólica , Sofosbuvir/efectos adversos , Sofosbuvir/sangre , Sofosbuvir/orina , Uridina/efectos adversos , Uridina/sangre , Uridina/farmacocinética , Uridina/orinaRESUMEN
In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7â¯nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8â¯nm, and mean centering of the ratio spectra (MCR) at 224â¯nm and 258â¯nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) µg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at pâ¯=â¯0.05.