Simultaneous estimation of donepezil and quercetin using ultra high performance liquid chromatography: pharmaceutical and pharmacokinetic applications in Alzheimer's disease.

Abstract

Background: Alzheimer's disease (AD) affects over 55.2 million individuals globally with current treatment modalities only providing symptomatic relief. This highlights the importance of combination therapies which target multiple pathways simultaneously. Donepezil (DNP), an acetylcholinesterase inhibitor, when combined with Quercetin (QCT), a polyhydroxy flavonoid with neuroprotective properties, might alter progression. However, simultaneous estimation of DNP and QCT for concurrent delivery, calls for robust analytical method that can simultaneously estimate both drugs.

Research design and methods: A simple, robust, and cost-friendly UHPLC method for simultaneous estimation of DNP and QCT was developed. The analytes were resolved on C18 column (Kromasil C18, 4.6 × 250 mm), with acetonitrile and 0.1% diethyl amine buffer, adjusted to pH 3.5 with glacial acetic acid as mobile phase in ratio 50:50 v/v at 0.6 mL/min, at column oven temperature 40°C in total analysis run time of 10 min.

Results: DNP and QCT were quantified by PDA detector at 268 nm and 370 nm, respectively. The developed method was found to be linear, accurate, precise, specific, and robust as per ICH guidelines.

Conclusion: The developed and validated method efficiently quantified DNP and QCT co-loaded inside liposomes estimating their entrapment efficiency, loading efficiency, and in vivo plasma kinetics.