Sensitive gas chromatographic–mass spectrometric method for the determination of gacyclidine in rat plasma and spinal cord dialyzates

Abstract

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 µl 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).

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