The main aim of the current work is to investigate possible pharmacokinetic interactions between vardenafil hydrochloride (VAR), which is used for the treatment of erectile dysfunction and daclatasvir dihydrochloride (DAC), which is used for the treatment of chronic hepatitis C viral infection when they are concomitantly administered. Therefore, a sensitive and selective square‐wave voltammetric method was developed and validated for simultaneous determination of VAR and DAC using disposable pencil graphite electrode (PGE) modified with xylenol orange (X.O.) flakes as an electrochemical sensor. A full investigation of the experimental parameters for obtaining the highest electroanalytical signal with sufficient resolution between the oxidation peaks of two compounds was performed. It was found that VAR and DAC were resolved on X.O./PGE with different potentials at 1.4 V and 0.9 V, respectively using Britton‐Robinson buffer (pH 2.2) and 0.1 mol L−1 KCl as a supporting electrolyte. In addition, with the aid of cyclic voltammetry, a mechanistic scheme for the oxidation behaviour of both VAR and DAC was suggested. The proposed square wave voltammetric method was successfully applied for trace quantification of VAR and DAC in male rabbits. The suggested approach shows detection and quantification limits in rabbit plasma samples of 0.06 and 0.17 μmol L−1, respectively for VAR and 0.13 and 0.39 μmol L−1, respectively for DAC. The pharmacokinetic parameters of VAR alone and in combination with DAC after oral administration to rabbits were successfully estimated. The obtained results confirm that when DAC is co‐administered with VAR, plasma concentration of VAR increases, which necessitates dose adjustment for VAR to prevent toxicological consequences in patients.
A novel MnO2 nanoparticles/chitosan-modified pencil graphite electrode (MnO2 NPs/CS/PGE) was constructed using two different MnO2 polymorphs (γ-MnO2 and ε-MnO2 nanoparticles).
Coadministration of tamoxifen citrate (TMC) and medroxyprogesterone acetate (MPA) is preferred to increase the response rate and the percentage recovery in patients with endometrial carcinoma. Administration of TMC and MPA and their combination affects estrogen and progestin receptor concentrations in advanced endometrium carcinoma by affecting 17β-hydroxyl steroid dehydrogenase activity and serum hormone concentrations. A sensitive, accurate and robust thin-layer chromatography method has been established for simultaneous analysis of TMC and MPA. Method development was carried out on silica gel F using butanol-acetic acid-water (6:0.5:0.5, v/v/v) as mobile phase. Densitometric scanning was carried out at 241 nm for simultaneous detection of TMC and MPA. Retardation factor (R ) values for TMC and MPA were 0.21 and 0.85, respectively. The method was validated according to ICH guidelines. Regression plots revealed linear relationships in the concentration range of 50-500 and 25-250 ng/band for TMC and MPA, successively. Accuracy was ≥99.60 and 98.72% for TMC and MPA, respectively. Forced degradation studies using UV photodegradation was applied on MPA after exposure to UV light for different times and applying a kinetic study for calculating the degradation rate constant (k) and half-life time (t ).
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