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 resolut ion of the enantiomers of E2020 (acetylcholinesterase inhibitor) in pl asma. This system employs two avidin columns and fast atom bombardment (FAB)-MS. A plasma sample was injected directly into an avidin trappi ng column (10 mm x 4.0 mm I.D.). The plasma protein was washed out fro m 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 spec ifically detected by FAB-MS without interference from metabolites of E 2020 and plasma constituents. The limit of quantification for each ena ntiomer of E2020 in plasma was 1.0 ng/ml and the intra- and inter-assa y relative standard deviations for the method were less than 5.2%. The assay was validated for enantioselective pharmacokinetic studies in t he dog.