A gas chromatographic/mass spectrometric assay for prenylamine suitable for pharmacokinetic studies of the racemate and the enantiomers

Abstract

A sensitive assay for prenylamine and dideuteroprenylamine (racemic or pseudo-racemate) has been developed and used in human pharmacokinetic studies. Plasma levels of prenylamine could be measured up to 50 h after a single oral therapeutic dose. The extracted drug was derivatized with pentafluoropropionic anhydride in acetonitrile. The dried samples were reconstituted in decane; an aliquot was injected into a fused-silica capillary in a cooled on-column injector. The base peaks in the electron impact mass spectra of the compounds--derived by loss of a benzyl radical--at m/z 384, 386 and 390 were measured for prenylamine, (D2)-prenylamine and the internal standard hexahydroprenylamine, respectively. The sensitivity of this assay--limit of detection 0.2 ng ml-1 plasma with a signal-to-noise ratio of 5:1--allowed measurement of the kinetics of the racemate and of both stereoisomers for the first time. In man, the (+)-isomer was eliminated considerably faster than the (-)-prenylamine; the area under the plasma concentration time curve (AUC) of the (+)-isomer was only about 1/4 of the AUC of (-)-prenylamine.