Development, application and validation of RP-HPLC method for the simultaneous determination of butamirate citrate and its main degradation product in pharmaceutical dosage forms

Abstract

A simple, rapid and sensitive reversed phase high performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous determination of butamirate citrate (BT) and its hydrolysis product (α-ethylbenzeneacetic acid (EA)). The method was based on HPLC separation of BT from its hydrolysis product using a Shim-pack cyanopropyl column (250 mm × 4.6 mm i.d., 5 μm particle diameter) at ambient temperature with the mobile phase consisting of acetonitrile–25 mM potassium dihydrogen phosphate, pH 3.4 (40 : 60, v/v). Quantitation was achieved with UV detection at 210 nm based on peak area. The method was validated with respect to specificity, linearity, limit of detection, limit of quantitation, accuracy, precision and robustness. The method was successfully applied for the determination of BT and its hydrolysis product in syrup. The proposed method was used to investigate the kinetics of acidic and alkaline hydrolysis processes of BT at different temperatures and the apparent pseudo-first-order rate constant, half-life and activation energy were calculated. The pH–rate profile of hydrolysis of BT in Britton–Robinson buffer solutions within the pH range 1.4–12 was studied.