الفهرس 
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Abstract
The thesis is devoted for developing new methods for determination of ribavirin, sofosbuvir and ledipasivir in pharmaceutical preparations. In addition to study the stability of these drugs in different storage conditions, temperatures and in dissolution medium (0.1 N HCl). The thesis comprises four main parts: Part I: Included a general introduction about antiviral drugs, the chemical and physical properties of the studied drugs. Part II: Method I: First derivative spectrophotometry for ledipasvir and sofosbuvir. Method II: Conventional dual wavelength method for sofosbuvir determination. Method III: Isosbestic point method for sofosbuvir determination. Method IV: Absorbance correction method for sofosbuvir determination Method V: Absorbance ratio method (Q-analysis) for sofosbuvir determination. Part III: The development and validation RP-HPLC method with dual detection by UV and florescence detectors for analysis of sofosbuvir and ledipasvir within 7 min. The proposed method was developed and optimized by 23 full factorial design. The mobile phase consisted of acetonitrile:methanol:0.01% triethylamine adjusted to pH 3 by glacial acetic acid [35: 35:30] (v/v/v). Part IV: The development and validation RP-HPLC-UV for analysis of sofosbuvir and ledipasvir with coadministered drug (ribavirin) within 10 min. The mobile phase consisted of methanol and 0.005 M Heptane-1-sulphonic acid sodium salt adjusted to pH 2.5. The developed method was applied to study the stability of these drugs in acidic medium and determine the kinetics of their acidic degradation process. The kinetic rate constant, half-life time and activation energy of the degradation reactions were calculated. Also, the in vitro interaction between RIB capsules with SOF/LED tablets in 0.1 N HCl (SGF) was estimated by our proposed method without predilution procedure. Finally; the greenness of the proposed method was estimated by eco-scale and GAPI guidelines. The validation criteria of the developed methods were intensively studied. All the results were statistically analyzed and compared with those given by comparison methods.