Donepezil hydrochloride

Donepezil hydrochloride (Figure 1a) was purchased from Tokyo Chemical Industry (Tokyo, Japan), and escitalopram oxalate (Figure 1b) was purchased from Sigma-Aldrich (Saint Louis, MO, USA). DMN patches were prepared in the Laboratory of Pharmaceutics, College of Pharmacy, Gyeongsang National University (Jinju, South Korea). Fisher Scientific (Hampton, NH, USA) provided HPLC-grade methanol, acetonitrile, and water (Seoul, South Korea). Methyl tert-butyl ether was purchased from Avantor Performance Materials (Center-Valley, PA, USA). Tegaderm™ film and Micropore™ surgical tape were purchased from 3M Healthcare (Saint Paul, MN, USA).

5-O-Desmethyldonepezil, 6-O-desmethyldonepezil, hydroxydonepezil, 3-hydroxydonepezil, donepezil N-oxide, and desbenzyldonepezil were supplied by Toronto Research Chemicals (Figure 1, Toronto, ON, Canada). Donepezil hydrochloride was purchased from Tokyo Chemical Industry (Tokyo, Japan). Potassium cyanide (KCN) and reduced L-glutathione (GSH) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Nicotinamide adenine dinucleotide phosphate reduced form (β-NADPH) was purchased from Oriental Yeast (Tokyo, Japan). Human liver microsomes (HLM (cytochrome P450, 0.411 nmol/mg protein; cytochrome b₅, 0.449 nmol/mg protein; and NADPH-cytochrome c reductase, 182 ± 11 nmol/mg protein/min), catalog No. H2630), mouse liver microsomes (MLM (cytochrome P450, 0.939 nmol/mg protein; cytochrome b₅, 0.414 nmol/mg protein; and NADPH-cytochrome c reductase, 138 ± 4 nmol/mg protein/min), catalog No. M1000), and rat liver microsomes (RLM (cytochrome P450, 0.646 nmol/mg protein; cytochrome b₅, 0.484 nmol/mg protein; and NADPH-cytochrome c reductase, 124 ± 8 nmol/mg protein/min), catalog No. R1000) were acquired from XenoTech (Lenexa, KS, USA). All solvents for liquid chromatography-MS were obtained from Fisher Scientific Co. (Pittsburgh, PA, USA) with the highest grade commercially available.