Sensitive gas chromatographic-mass spectrometric method for the determination of gacyclidine in rat plasma and spinal cord dialyzates.
A sensitive gas chromatographic-mass spectrometric (GC-MS) procedure is described for the selective determination of gacyclidine (a non-competitive N-methyl-D-aspartate antagonist) in rat plasma and spinal cord dialyzates. It involves a single-step liquid-liquid extraction of plasma samples and dialyzates with hexane (pH 8.0) and the use of phencyclidine as an internal standard. The compounds were separated on a GC capillary column and specifically detected by MS in the selected-ion monitoring mode. Gacyclidine and its internal standard were monitored by using the fragment ions at m/z 206 and 200, respectively. The method was accurate and reproducible (intra- and inter-day reproducibility < 12%) with a limit of quantification of 1.6 ng ml-1 using 100 microliters plasma of dialyzate samples. The calibration curves for rat plasma and Ringer's solution were linear (r2 > 0.996) over a range from 1.6 to 200 ng ml-1. The extraction efficiency was close to 100%. This simple and rapid assay (total run time < 10 min) was validated for a pilot pharmacokinetic study in healthy rats after intravenous injection of a bolus dose of gacyclidine (2.5 mg kg-1).
Hoizey
G
G
Laboratoire de Pharmacologie et de Pharmacocinétique, UFR de Pharmacie, Université de Reims Champagne Ardenne, France. guillaume.hoizey@univ-reims.fr
Lamiable
D
D
Dukic
S
S
Millart
H
H
d'Arbigny
P
P
Vistelle
R
R
D000818:Animals; D003510:Cyclohexanes / Q000097:blood* / Q000134:cerebrospinal fluid; D053138:Cyclohexenes; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000097:blood* / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D003510:Cyclohexanes; D053138:Cyclohexenes; D010880:Piperidines; D016202:N-Methylaspartate; C070707:gacyclidine