Chromatographic methods for the determination of butamirate citrate in presence of its degradation product

Abstract

Two chromatographic methods were applied for the determination of butamirate citrate (BC) drug in the presence of its degradation product. Rapid resolution liquid chromatography (RRLC) Agilent SB-C18 (4.6 × 50 mm, 1.8 µm) column with mobile phase [0.2% triethyl amine buffer:acetonitrile (50:50 v/v)], pH 4.8 adjusted with phosphoric acid and ultraviolet detection at 222 nm was the first method. HPLC Promosil C18 (4.6 mm × 250 mm, 5 μm) column with mobile phase [0.05 M ammonium dihydrogen phosphate buffer:acetonitrile 50:50 (v/v)] with pH 5.4 and ultraviolet detection at 222 nm was the second method. These methods showed high sensitivity concerning linearity, accuracy, and precision over the range from 5 to 150 µg mL⁻¹ and 1 to 150 µg mL⁻¹ for RRLC and HPLC methods, respectively. The proposed methods were successfully applied for the determination of butamirate citrate (BC) in its commercial formulation (cough cut syrup). The International Conference on Harmonization guidelines (ICH) were adopted for methods’ validation with respect to linearity, LOD, LOQ, precision and specificity. Moreover, to establish stability-indicating capability of the proposed methods, the kinetics of degradation of BC were studied in aqueous alkaline and acidic solution. The thermodynamic parameters of activation (enthalpy, free energy and entropy) were determined for acidic degradation reaction and half-life times could also be estimated.