Simultaneous Determination Of Ledipasvir Research Articles

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.

Application of TLC Densitometric Method for Simultaneous Estimation of the Newly Co-formulated Antiviral Agents Ledipasvir and Sofosbuvir in Their Tablet Dosage Form

Ledipasvir (LED) and Sofosbuvir (SOF) are newly approved antiviral agents co-formulated for treatment of hepatitis C virus. In the present work; an accurate and precise TLC densitometric method has been developed for simultaneous determination of LED and SOF in their bulk and dosage form. The proposed method based on determination of the UV-visualized bands after TLC separation of LED and SOF. The studied drugs were quantitatively separated on 60 F254 silica gel plates using mobile phase consists of (90% ethyl acetate: 9% hexane: 1% tri ethylamine by volume) with UV detection at 250 nm. The studied drugs were satisfactorily resolved with retention factor (Rf) values of 0.09 ± 0.005 and 0.23 ± 0.01 for LED and SOF, respectively. The proposed method has been validated according to ICH guidelines and show high sensitivity, accuracy and precision and the results were statistically compared to reported method.

Simultaneous determination of ledipasvir, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.

In this work, a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ledipasvir, sofosbuvir and its metabolite GS-331007 in rat plasma was developed. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 889.8→130.1 for ledipasvir, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 2-500ng/mL for ledipasvir, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatography was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<10.2% and the accuracy values ranged from -9.8% to 11.2%. The method was successfully applied to a pharmacokinetic study of ledipasvir, sofosbuvir and GS-331007 in rats.