Development of a green stability-indicating HPLC–DAD method for the determination of donepezil hydrochloride in the presence of its related substance and degradation products

Abstract

ABSTRACTA simple, eco-friendly, stability-indicating HPLC method was developed for the determination of donepezil hydrochloride (DH) in tablet dosage form in the presence of its pharmacopoeia-related compound (donepezil-related compound A) and its different degradation products. The chromatographic conditions were optimized to achieve the highest performance parameters using Zorbax Eclipse Plus C18 rapid resolution column (4.6 × 100 mm, 3.5 µm), with a mobile phase composed of 72.5% acetate buffer pH 5.5 and 27.5% ethanol, flowing at 1 mL min−1. The diode array detector (DAD) was set at 315 nm and the column oven was adjusted at 45°C. Linear response (r = 0.9999) was observed over the range of 2–28 µg mL−1 of donepezil, with detection and quantitation limits of 0.031 and 0.103 µg mL−1, respectively. Forced degradation studies were performed on standard DH and test Demepezil® 5-mg tablets under various conditions and the method was found to be stability indicating. The purity of DH peak was confirmed using the DAD. In the developed method, two principles of green chromatography were adopted (reduce and replace) by reducing solvent consumption through the utilization of a short column (10 cm) with a smaller particle size (3.5 µm) instead of a normal 25 cm with a 5 µm particle size and by replacing hazardous solvents of the official United States Pharmacopoeia method as acetonitrile with ethanol. Furthermore, the greenness of the method was assessed using three assessment tools.