Simultaneous determination of donepezil, 6-O-desmethyl donepezil and spinosin in beagle dog plasma using liquid chromatography‒tandem mass spectrometry and its application to a drug-drug interaction study

Publication date: Available online 13 October 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Chae Bin Lee, Jee Sun Min, Soon Uk Chae, Hye Min Kim, Jun Hee Jang, In Ho Jung, Yu Fen Zheng, Jong Hoon Ryu, Soo Kyung BaeABSTRACTSpinosin, which is traditionally used for sedation and sleep disorders, has recently shown potential effects in alleviating memory loss. As spinosin is the main bioactive component in a standardized dried 50% ethanol extract of the seeds of Zizyphus jujuba var. spinosa, a Phase Ⅱb clinical trial is ongoing, in Korea for the combination of the above extract formulated in a tablet (DHP1401 tablet) with donepezil hydrochloride (Aricept® tablet) in patients with mild to moderate Alzheimer’s disease. Therefore, to promote safety and efficacy evaluations, a reliable method for the simultaneous detection and analysis of the two drugs is needed. Toward this end, in this study, we established and validated a rapid and sensitive LC‒MS/MS method for the simultaneous determination of donepezil, its pharmacologically active metabolite 6-O-desmethyl donepezil, and spinosin in beagle dog plasma (50 μL). After optimization of the system, we used methanol for simple protein precipitation. Chromatographic separation was performed using a Phenomenex Luna C18 column (100 × 2.0 mm, 3 μm) with a mobile phase consisting of 0.1% formic acid in acetonitrile-0.1% formic acid in distilled water (2:8, v/v) at a flow rate of 0.65 mL/min. A...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research