Rizzo M.^*, Sinopoli V.A.^**, De Sarro G.^**, Ricci P.^***

^*Chair of Chemistry, School of Pharmacy, University of Reggio Calabria, Italy
^**Chair of Pharmacology. Department of Experimental and Clinical Medicine,University of Reggio Calabria, Italy
^***Chair of Legal Medicine, Department of Experimental and Clinical Medicine, University of Reggio Calabria, Italy

Recently 2,3 benzodiazepine derivatives (2,3-BZs) synthesized in our laboratories were shown to have marked anticonvulsant activity in various models of seizures (1).
Some compounds showed comparable or better activity than GYKI 52466 and appeared to be more potent than NBQX. The biological results suggest that 2,3-BZs act as non comparative AMPA-receptor antagonists and do not affect GABA-A receptor mediated responses. In order to develop an assay suitable for pharmocokinetic studies, we report herein a sensitivity, specific and rapid liquid-chromatographic method for determination of the above mentioned 2,3-BZs and their metabolites.
The 2,3-BZs were dissolved in a solution containing 50% dimethylsulfoxide and 50% sterile saline, and administered intraperitoneally (i.p.) to Sprague-Dawley rats (10 mg/kg of body weight). Plasma was collected 15, 30, 45, 60 and 90 minutes after administration of drugs.
The drugs were isolated from plasma by a double step extraction, with the use of prazepam as internal standard (I.S.) for quantitative determination.
A reverse phase column was utilized (C18 Ultrasphere), with an isocratic mobile phase or methanol-water (65:35), at a flow rate 1.5 ml/min, with ultraviolet detection at 254 nm.
Plasma levels of approximately 10 ng/mL can be measured with as little as 500 µl of plasma.
Preliminary results will be presented and discussed.

References

1. De Sarro G., Chimirri A., De Sarro A., Gitto R., Grasso S., Giusti P., Chapman A.G., Eur. J. Pharmacol, 1995, 294, 411.