DEVELOPMENT OF A STABILITY-INDICATING HPLC METHOD FOR THE DETERMINATION OF MONTELUKAST IN TABLETS AND HUMAN PLASMA AND ITS APPLICATIONS TO PHARMACOKINETIC AND STABILITY STUDIES

Abstract

A stability-indicating high performance liquid chromatographic (HPLC) method has been developed and validated for the determination of montelukast in human plasma and in its pharmaceutical dosage from. The proposed method has been also applied for the determination of montelukast in the presence of its degradation product. Acetonitrile: potassium dihydrogen phosphate (0.05 M) adjusted to pH 3.5 ± 0.1 with phosphoric acid (70:30, % v/v) was used as the mobile phase at a flow rate of 2.0 ml/min using a Symmetry C18 column. The effluent was spectrophotometrically monitored at 345 nm. Peak area ratio of the drug to the internal standard (flufenamic acid) was used for the quantification of montelukast in plasma samples and the limit of quantification was 10 ng/ml and the limit of detection was 1.0 ng/ml. The intraday and interday precisions showed coefficients of variation ranged from 5.87 % to 9.60 % and from 2.13 % to 6.18 % at three different levels of concentrations. The averages of the absolute and relative recoveries were found to be 94.7 to 98.0 % and 95.5 to 97.5%, respectively. The pharmacokinetic parameters of montelukast after intravenous administration of 10 mg solution to five rabbits were determined. The proposed HPLC method was successfully applied to study the degradation kinetics of montelukast. The photodegradation kinetics of montelukast in methanolic solution