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 has been developed for the simultaneous quantitation of the enantiomers of (+/-)-gacyclidine (a non competitive N-methyl-D-aspartate antagonist) in human plasma. Gacyclidine enantiomers and phencyclidine (PCP), the internal standard, were extracted using a single-step liquid-liquid 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. Gacyclidine enantiomers and PCP were monitored using the fragment ions at m/z 206 and 200, respectively. No interference was observed from endogenous components. The limit of quantitation (LOQ) for each enantiomer of gacyclidine was 300 pg/ml by using plasma samples of 500 microl. The calibration curves were linear (r2=0.998) over a range of 0.3125 to 20 ng/ml. The extraction efficiency was higher than 95% for both enantiomers. Intra- and inter-day bias were less than 10% at every standard curve concentration. Intra-day precision was less than 19% for (-)-gacyclidine 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.
Hoizey
G
G
Laboratoire de Pharmacologie et de Pharmacocinétique, U.F.R. de Pharmacie, Reims, France.
Vistelle
R
R
Lamiable
D
D
Millart
H
H
Gourdier
B
B
d'Arbigny
P
P
D002138:Calibration; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008832:Microchemistry; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D011786:Quality Control; D012680:Sensitivity and Specificity; D012997:Solvents; D013237:Stereoisomerism
D012997:Solvents; D016202:N-Methylaspartate; C012058:tenocyclidine; D010622:Phencyclidine