doiSerbia

Quantitative analysis of Loperamide hydrochloride in the presence its acid degradation products

Savić Ivana M. (Tehnološki fakultet, Leskovac)
Nikolić Goran S. (Tehnološki fakultet, Leskovac)
Savić Ivan M. (Tehnološki fakultet, Leskovac)
Marinković Valentina D. (Farmaceutsko-hemijska industrija 'Zdravlje-Actavis', Leskovac)

The aim of this work was to develop a new RP-HPLC method for the determination of loperamide hydrochloride in the presence of its acid degradation products. Separation of loperamide from degradation products was performed using ZORBAX Eclipse XDB C-18, column with a mobile phase consisting of 0.1% sodium-octansulphonate, 0.05% triethylamine, 0.1% ammonium hydroxide in water:acetonitrile (45:55 v/v). The mobile phase was adjusted to pH 3.2 with phosphoric acid. The method showed high sensitivity with good linearity over the concentration range of 10 to 100 μg cm-3. The method was successfully applied to the analysis of a pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia) containing loperamide hydrochloride with excellent recovery. The loperamide hydrochloride degradation during acid hydrolysis and kinetics investigation was carried out in hydrochloric acid solutions of 0.1, 1.0 and 1.5 mol dm-3, at different temperatures (25 and 40°C), by monitoring the parent compound itself. The first order reaction of loperamide degradation in acid solution was determined. The activation energy was estimated from the Arrhenius plot and it was found to be 38.81 kJ mol-1 at 40°C. The developed procedure was successfully applied for the rapid determination of loperamide hydrochloride in pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia) and in the presence of its acid degradation products.

Keywords: Loperamid hydrochloride, degradation products, HPLC, kinetics