DETERMINATION OF GACYCLIDINE ENANTIOMERS IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY USING SELECTED-ION MONITORING

A sensitive gas chromatographic assay using mass selective-detection h as been developed for the simultaneous quantitation of the enantiomers of (+/-)-gacyclidine (a non competitive N-methyl-D-aspartate antagoni st) in human plasma. Gacyclidine enantiomers and phencyclidine (PCP), the internal standard, were extracted using a single-step liquid-liqui d extraction with hexane at pH 8.0. Each enantiomer was separated on a chiral gas chromatography capillary column and specifically detected by mass spectrometry (MS) in selected-ion monitoring (SIM) mode. Gacyc lidine enantiomers and PCP were monitored using the fragment ions at m /z 206 and 200, respectively. No interference was observed from endoge nous components. The limit of quantitation (LOQ) for each enantiomer o f gacyclidine was 300 pg/ml by using plasma samples of 500 mu l. The c alibration curves were linear (r(2)=0.998) over a range of 0.3125 to 2 0 ng/ml. The extraction efficiency was higher than 95% for both enanti omers. Intra-and inter-day bias were less than 10% at every standard c urve concentration. Intra-day precision was less than 19% for (-)-gacy clidine and 15% for (+)-gacyclidine. Inter-day precision was below 15% for both enantiomers. The assay was validated for an enantioselective pharmacokinetic study in healthy male volunteers. (C) 1997 Elsevier S cience B.V.