Simultaneous Determination Of Sofosbuvir Research Articles

Development and Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Sofosbuvir, Velpatasvir, and Voxilaprevir in Tablet Formulation

Objective: The present study aimed to develop a stability-indicating reverse-phase high performance-liquid chromatography (RP-HPLC) method for the estimation of Sofosbuvir, Velpatasvir, and Voxilaprevir in tablet dosage form and validated in accordance with ICH guidelines. Methods: The optimized conditions for the developed RP-HPLC method are Agilent C18 (250 mm×4.6mm, 5μ) column maintained at 30ºC with a mobile phase consisting of Buffer(0.1%OPA) and Acetonitrile taken in the ratio 55:45%v/v on isocratic mode at flow rate 1.0ml/min. The sample was detected at 220 nm. Results: The retention time of Sofosbuvir, Velpatasvir, and Voxilaprevir was found to be 2.17, 2.731 and 3.55 min respectively. The developed method was validated for accuracy, precision, specificity, ruggedness, robustness and solution stability.

Two novel UPLC methods utilizing two different analytical columns and different detection approaches for the simultaneous analysis of velpatasvir and sofosbuvir: application to their co-formulated tablet

In the present study two different RSLC columns, Acclaim RSLC 120 C18, 5.0 µm, 4.6 × 150 mm (column A) and Acclaim RSLC 120 C18, 2.2 µm, 2.1 × 100 mm (Column B) were utilized for the analysis of velpatasvir (VPS) in presence of sofosbuvir (SFV), where due to the encountered fluorescent properties of VPS fluorescent detection at 405 nm after excitation at 340 nm (Method 1) was used for its detection where the non-fluorescent SFV did not interfere. The same columns were further utilized for the simultaneous determination of SFV and VPS either in bulk form or in their combined tablet, where UV- spectrophotometric detection at 260 nm was selected for the simultaneous analysis of both drugs (Method 2). A mobile phase consisting of NaH2PO4, pH 2.5 (with phosphoric acid) and acetonitrile in a ratio of 60:40 v/v was used for both methods. The mobile phase was pumped at a flow rate of 1.0 mL/min when using column, A and 0.5 mL/min when using column B. The methods showed good linearity over the concentration ranges of 1.0–5.0 and 2.5–10.0 ng/mL for VPS when utilizing Method 1 A and B respectively. Where the linearity concentration range was from 30.0–150.0 to 120–600.0 ng/mL for VPS and SFV respectively when applying Method 2. Both methods 1 and 2 were performed by utilizing the two analytical columns. The different chromatographic parameters as retention time, resolution, number of theoretical plates (N), capacity factor, tailing factor and selectivity were carefully optimized. The results show that comparing the performance of the two utilized columns revealed that shorter column (2.1 mm × 100 mm) with small particle packing was superior to the longer column (4.6 × 150 mm) for the analysis of the studied drugs allowing a reduction of the analysis time by 70% without any detrimental effect on performance. This prompts the decrease of the investigation costs by saving money on organic solvents and expanding the overall number of analyses per day.

New strategy for determination of anti-viral drugs based on highly conductive layered composite of MnO2/graphene/ionic liquid crystal/carbon nanotubes

In the last decade, the biomedical field has benefited from the progressive development of antiviral drugs. Antiviral drugs Sofosbuvir (SOF), ledipasvir (LED) and acyclovir (ACY) are a class of medications used specifically for treating viral infections as hepatitis C (HCV) and B (HBV) viruses. Sofosbuvir (SOF) and ledipasvir (LED) in a single-tablet regimen represent a revolution in the treatment of chronic hepatitis C which inhibits viral production of HCV. The major problem with simultaneous determination of SOF, LED and ACY by electrochemical methods is the closeness of their oxidation potentials resulting in overlapped voltammetry responses. In such frame an innovative strategy is introduced, based on a novel GC/CNT/ILC/RGO/MnO2 layered electrode, obtained by modifying a glassy carbon surface with layers of multi-walled carbon nanotubes (CNT), an ionic liquid crystal (ILC), graphene (RGO) and MnO2. The layered sensor showed excellent current responses for the simultaneous electrochemical analysis of SOF, LED and ACY in human serum in the concentration ranges 0.20–150μmoldm−3, 0.0070–15μmoldm−3 and 0.010–30μmoldm−3 with low detection limit values of 9.8nmoldm−3, 0.11nmoldm−3 and 0.84nmoldm−3 respectively. Moreover, on the new layered electrode the electro-oxidation of a quinary mixture of ascorbic acid (AA), dopamine (DA), paracetamol (APAP), SOF and LED yielded five well-separated peaks. This electrochemical method is advantageous over other methods mentioned in the literature in terms of cost, time effectiveness, sensitivity, selectivity and lower detection limit. Analysis of ACY and a combination from LED and SOF in their pharmaceutical formulations were achieved with good recovery results.

Development of a highly sensitive high-performance thin-layer chromatography method for the screening and simultaneous determination of sofosbuvir, daclatasvir, and ledipasvir in their pure forms and their different pharmaceutical formulations.

The combination of sofosbuvir and daclatasvir or sofosbuvir and ledipasvir is now widely used as an ideal treatment for hepatitis C virus infection. For this purpose, a simple, sensitive, accurate, economic, and precise high-performance thin-layer chromatography was developed and validated for the determination of sofosbuvir, daclatasvir, and ledipasvir in their pure form as well as their different pharmaceutical products. The method used Merck high-performance thin-layer chromatography aluminum plates precoated with silica gel 60 F254 as a stationary phase and mobile phase consisting of methylene chloride/methanol/ethyl acetate/ammonia (25%) (6:1:4:1, v/v/v/v). This system was found to give compact symmetric peaks of sofosbuvir, daclatasvir, and ledipasvir with retardation factors of 0.27 ± 0.01, 0.50 ± 0.007, and 0.68 ± 0.008, respectively. The densitometric scanner was set at 275nm using a deuterium lamp. The calibration curves were linear over the range of 100-3000ng/spot for sofosbuvir, and daclatasvir, and range of 50-3000ng/spot for ledipasvir. The detection limits were 22.5, 31.90, and 15.80 for sofosbuvir, daclatasvir, and ledipasvir. The quantitation limits were 67.50, 95.60, and 47.50 for sofosbuvir, daclatasvir, and ledipasvir. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines and the results were acceptable.

Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure form, human plasma and human urine using micellar monolithic HPLC-UV method and application to pharmacokinetic study

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. 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. Separation and quantitation were carried out on anonyx™ C8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 μL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50–400, and 40–400 ng/mL, respectively in pure form, 60–300 and 50–300 ng/mL, respectively for human plasma and over 50–400, and 40–400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences.

New stability indicating RP-UFLC method for the simultaneous determination of Velpatasvir and Sofosbuvir in tablets

A new liquid chromatographic method has been developed for the simultaneous determination of Sofosbuvir and Velpatasvir in oral dosage forms. Shimadzu Model CBM-20A/20 Alite with C8 (Phenomenex) column (250 mm × 4.6 mm i.d., 5 µm particle size) was used for the chromatographic study. Linearity was observed over the concentration range 4.54-400.14 µg/ml and 1.09-100.36 µg/ml with regression equations y = 26855x + 83874 (correlation coefficient 0.9997) and y = 35840x + 8543.8 (correlation coefficient 0.9999) for Sofosbuvir and Velpatasvir respectively. Sofosbuvir and Velpatasvir were subjected to forced degradation and the method was validated as per ICH guidelines.

Multivariate Chemometric Models and Application of Genetic Algorithm for Simultaneous Determination of Ledipasvir and Sofosbuvir in Pure Form and in Pharmaceutical Preparation; A Comparative Study

Objectives: Four multivariate chemometric methods have been developed for simultaneous determination of sofosbuvir and ledipasvir in their pure and pharmaceutical dosage forms. Methods: Firstly, partial least squares and artificial neural network have been applied for the quantitative analysis of the studied drugs. Results: Experimental design of different synthetic mixtures of sofosbuvir and ledipasvir in different ratios has been done. The zero-order absorption spectra of these prepared mixtures have been recorded over the wavelength range 200-400 nm with 1 nm interval. The obtained absorbance and concentration data matrix have been utilized to obtain calibration or regression analysis data which has been used for the prediction of the unknown concentrations of each drug in their mixtures. Alternatively, the application of genetic algorithm to partial least squares and artificial neural network has been done and greatly increased the precision and predictive ability of the methods. The four methods have been successfully applied to quantify sofosbuvir and ledipasvir in the real market sample. Conclusion: The investigated methods have been found to be accurate, precise and could resolve the overlapped spectra of the mixture without any preliminary separation steps.