In vivo microdialysis and thermospray tandem mass spectrometry of the dopamine uptake blocker 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR-12909)

Abstract

Microdialysis in conjunction with thermospray tandem mass spectrometry was employed in following the time course of the experimental drug GBB-12909 in vivo. GBR-12909 is 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-3-(phenylpropyl)-piperazine. An important feature of microdialysis exploited in the method is the elimination of sample cleanup procedures. The detection limit was determined to be 100 pg and the relative standard deviation of estimates for standard solution in the range of 50 nmol/L to 1 .mu.mol/L concentrations was found to be 17.degree.. Important factors in obtaining high sensitivity and reproductivity were carrier phase composition and operation in the flow injection mode. The maximum concentration of GBR-12909 in the brain for a dose of 100 mg/kg I.p. was determined to be 250 nmol/L with the maximumal concentration occurring approximately 2 h postinjection. This representa a 40-fold lower concentration of GBB-12909 in the brain as compared to cocaine concentration obtained at a dose of 30 mg/kg, which was estimated earlier under similar experimental conditions. This observation could explain the discrepancy between relative in vivo and in vitro potencies of the two drugs.