Oseltamivir is an antiviral drug used in the treatment and prophylaxis of influenza virus A and B infections. It was developed by Gilead Sciences and is currently marketed by Haffmann-La Roche (Roche) under the trade name Tamiflu. Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate. It is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. Oseltamivir carboxylate is eliminated entirely by renal excretion. Less than 20% of an oral radiolabeled dose is eliminated in feces.1) Chemically it is (3R,4R,5S)-4-acetylamino-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid, ethyl ester. 2)Stability testing forms an important part of the process of drug product development. The purpose of stability testing is to provide evidence on how the quality of a drug substance varies with time under the influence of a variety of environmental factors such as temperature, humidity and light, and enables recommendation of storage conditions, retest periods, and shelf life to be established. The assay of oseltamivir API (Active Pharmaceutical Ingredient) in stability test sample needs to be determined using stability indicating method, as recommended by the International Conference on Harmonization (ICH) guidelines 3) and USP.4)The present work was designed to develop a simple, precise and rapid analytical LC procedure, which would serve as stability indicating assay method for analysis of oseltamivir API. Literature survey for oseltamivir analysis revealed several methods based on different techniques, viz. LC-MS assay for it's quantification in plasma and urine, 5) LC assay for evaluation of Tamiflu 6) and HPLC method for the determination of oseltamivir in Tamiflu. 7)The present study is the first time report on stability indicating assay of oseltamivir in presence of degradation products by HPLC. In this method gradient elution method is selected for the analysis of oseltamivir API because it gave better base line separation and peak width, which is suitable for the routine analysis of oseltamivir. Although the gradient elution method uses two-pump system, the gradient run provided a proper peak with baseline, which prompted us to select this method for the analysis of oseltamivir API.In view of above in the present study we hereby report the development and validation of a stability indicating gradient reverse-phase HPLC (RP-HPLC) method for analysis of oseltamivir API in presence of degradation products as per ICH guidelines.In order to establish the stability indicating nature of the method, force degradation of oseltamivir was performed under various stress conditions (basic, acidic and oxidative), and stressed samples were analyzed by the proposed method. The proposed LC method was able to separate the drug from degradation products generated during forced degradation studies. The developed method was validated as per ICH guidelines 8) and its updated international convention.9) The linearity of response, preci...

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A stability-indicating ultra-performance liquid chromatography method was developed and validated for the simultaneous determination of a fixed dose combination of atorvastatin and ezetimibe in bulk drugs. The developed method was successfully applied to the simultaneous quantitative analysis of the combination drugs in tablet. The chromatographic separation was performed on a Kromasil Eternity C18 UHPLC column (2.5 µm, 2.1 × 50 mm) using a gradient elution of acetonitrile and ammonium acetate buffer (pH 6.70; 0.01M) as the mobile phase at a flow rate of 0.2 mL/min with column oven temperature of 40°C. Ultraviolet detection was performed at 245 nm. Total run time was 5 min, within which the primary compounds and their degradation products were separated. The method was validated for accuracy, repeatability, reproducibility and robustness. Linearity, limit of detection and limit of quantitation were established for atorvastatin and ezetimibe.

A simple, specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of losartan potassium and ramipril in table dosage forms. A hypersil ODS C18, 4.6×250 mm, 5 μm column in isocratic mode, with mobile phase acetonitrile:methanol:10 mM tetra butyl ammonium hydrogen sulphate in water in the ratio of 30:30:40% v/v/v was used. The flow rate was 1.0 ml/min and effluent was monitored at 210 nm. The retention times of losartan potassium and ramipril were 4.7 and 3.3 min, respectively. The linearity range for losartan potassium and ramipril were in the range of 0.04-100 μg/ml and 0.2-300 μg/ml, respectively. The proposed method was also validated and successfully applied to the estimation of losartan potassium and ramipril in combined tablet formulations.