Aymen Labidi

Bio: Aymen Labidi is an academic researcher from Tunis University. The author has contributed to research in topics: Ledipasvir & Daclatasvir. The author has an hindex of 1, co-authored 2 publications receiving 2 citations.

Chemometrically Assisted Development of Ultra-High-Performance Liquid Chromatography Method for the Simultaneous Quantification of Sofosbuvir, Daclatasvir and Ledipasvir in Pharmaceutical Dosage Forms

Abstract: A new ultra-high-performance liquid chromatography method for the simultaneous quantification of sofosbuvir, daclatasvir and ledipasvir was developed. Two combinations of these direct-acting antivirals are used in hepatitis C virus infection therapy and show high efficacy and safety. Fractional factorial design was used for screening the most influential factors on separation and time analysis. These significant factors were optimized using a central composite design. The optimum resolution was carried out by using a Waters XBridge C18 column (150 mm, 4.6 mm ID, 5 μm) at a temperature of 35°C ± 2°C and acetonitrile/sodium perchlorate buffer (10 mM, pH = 3.2) (40: 60 v/v) as mobile phase at a flow rate of 1.5 mL min-1. UV detection was set at λ = 210 nm. A short chromatographic separation time was achieved. The developed method was validated according to the accuracy profile approach and was found specific, precise, faithful and accurate. The detection limits were between 0.07 and 0.13 μg mL-1. Hence, this novel method can be employed for the routine quality control analysis and in dissolution profile studies of generics containing these products.

RP-HPLC Stability Indicating Method Development and Validation for Simultaneous Determination of Grazoprevir and Elbasvir

Abstract: Elbasvir (ELB) and grazoprevir (GZP) were two new approved drugs and their co-formulation presents one of the more recently approved combinations for treatment of hepatitis C virus. A stability indicating reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of ELB and GZP and their degradation products under hydrolysis and oxidative stress conditions as per International Conference on Harmonization [ICH Q1A (R2) guidelines]. Adequate chromatographic separation with well-defined peaks was achieved using a Waters Spherisorb phenyl Column (150 mm × 4.6 mm I.D, 5 µm particle size) with a temperature maintained at 40 °C ± 2 °C. The mobile phase consists of acetonitrile: 5 mM ammonium formate buffer (+ 0.1% v/v of trimethylamin, pH was adjusted to 3.2 by formic acid) (60:40 v/v) at a flow rate of 0.8 mL min−1. A validation study was performed according to the accuracy profile methodology. Specificity, suitability, robustness, precision and trueness of the developed method were confirmed. The proposed method was also successfully compatible to identification of molecular structure of degradation products by liquid chromatography-mass spectrometry (LC–MS) coupling. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization source was used to characterizing degradation products based on the MS spectra and accurate mass measurements.

A Review on Analytical Strategies for the Assessment of Recently Approved Direct Acting Antiviral Drugs.

Abstract: Human beings are in dire need of developing an efficient treatment against fierce viruses like hepatitis C virus (HCV) and Coronavirus (COVID-19). These viruses have already caused the death of over two million people all over the world. Therefore, over the last years, many direct-acting antiviral drugs (DAADs) were developed targeting nonstructural proteins of these two viruses. Among these DAADs, several drugs were found more effective and safer than the others as sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir. The last one is indicated for COVID-19, while the rest are indicated for HCV treatment. Due to the valuable impact of these DAADs, larger number of analytical methods were required to meet the needs of the clinical studies. Therefore, this review will highlight the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites. These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.

RP-HPLC Stability Indicating Method Development and Validation for Simultaneous Determination of Grazoprevir and Elbasvir

Abstract: Elbasvir (ELB) and grazoprevir (GZP) were two new approved drugs and their co-formulation presents one of the more recently approved combinations for treatment of hepatitis C virus. A stability indicating reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of ELB and GZP and their degradation products under hydrolysis and oxidative stress conditions as per International Conference on Harmonization [ICH Q1A (R2) guidelines]. Adequate chromatographic separation with well-defined peaks was achieved using a Waters Spherisorb phenyl Column (150 mm × 4.6 mm I.D, 5 µm particle size) with a temperature maintained at 40 °C ± 2 °C. The mobile phase consists of acetonitrile: 5 mM ammonium formate buffer (+ 0.1% v/v of trimethylamin, pH was adjusted to 3.2 by formic acid) (60:40 v/v) at a flow rate of 0.8 mL min−1. A validation study was performed according to the accuracy profile methodology. Specificity, suitability, robustness, precision and trueness of the developed method were confirmed. The proposed method was also successfully compatible to identification of molecular structure of degradation products by liquid chromatography-mass spectrometry (LC–MS) coupling. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization source was used to characterizing degradation products based on the MS spectra and accurate mass measurements.