Direct determination of E2020 enantiomers in plasma by liquid chromatography-mass spectrometry and column-switching techniques.
High-performance liquid chromatography with column switching and mass spectrometry (MS) was applied to the on-line determination and resolution of the enantiomers of E2020 (acetylcholinesterase inhibitor) in plasma. This system employs two avidin columns and fast atom bombardment (FAB)-MS. A plasma sample was injected directly into an avidin trapping column (10 mm x 4.0 mm I.D.). The plasma protein was washed out from the trapping column immediately while E2020 was retained. After the column-switching procedure, E2020 was separated enantioselectivity in an avidin analytical column. The separated E2020 enantiomers were specifically detected by FAB-MS without interference from metabolites of E2020 and plasma constituents. The limit of quantification for each enantiomer of E2020 in plasma was 1.0 ng/ml and the intra- and inter-assay relative standard deviations for the method were less than 5.2%. The assay was validated for enantioselective pharmacokinetic studies in the dog.
Matsui
K
K
Department of Drug Metabolism and Pharmacokinetics, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibarak, Japan.
Oda
Y
Y
Ohe
H
H
Tanaka
S
S
Asakawa
N
N
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D000077265:Donepezil; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007189:Indans / Q000097:blood* / Q000737:chemistry; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil