Nitroproston is an innovation multitarget pharmaceutical based on natural prostaglandin and dinitroglycerol moety. The drug was developed for treatment of obstructive diseases in lungs including asthma and obstructive bronchitis. The goal of the presented study was to develop and validate a method for quantitative analysis of nitroproston and its main metabolites in rabbit’s plasma and its application for pharmacokinetic study of the drug. Sample preparation contained liquid-liquid extraction with ethyl acetate. For the instrumental method there was chosen high performance liquid chromatography – mass spectrometric technique that allowed to perform a quantitative analysis of the drug with high rates of accuracy and selectivity. Validation of the developed method was assessed for such parameters as: selectivity, low limit of quantification, linearity, precision and accuracy, recovery, matrix effect and stability. The method was further applied for study of pharmacokinetic parameters of nitroproston and its metabolites in rabbit’s plasma. For this purpose, six rabbits were intravenously administered with nitroproston in the dose of 25 mg/kg, where other six rabbits represented control group. Plasma samples were taken in 2, 4, 6, 4, 8, 12, 18, 24, 32 and 60 minutes after.
Due to active biodegradation of nitroproston, the method was also validated for main metabolites of the drug that showed high levels of stability. As the result of the conducted validation, it was found that the method in valid for the assessed parameters. At the same time, Pharmacokinetic study of the metabolites showed that reliable profiles were received for 1,3-dinitroglycerol (first phase metabolite) and 13,14-dihydro-15keto-PGE2 (second phase metabolite).
Method Development and Validation of a Stability-Indicating RP-HPLC Method for the Quantitative Analysis of Dronedarone Hydrochloride in Pharmaceutical Tablets
