Analytical Chemistry and Spectroscopy
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
A procedure which utilizes the specificity of tandem mass spectrometry was developed for the simultaneous quantification of fluphenazine and its stable isotopomer, [2H4] fluphenazine, in 1 ml plasma samples, after low oral doses of this antipsychotic agent. The unlabeled and the deuterium labeled-drug were isolated by a selective extraction procedure, derivatized and analyzed under electron impact ionization via the direct insertion probe of a tandem mass spectrometer. Selected reaction monitoring of the low-energy collision-induced dissociation of analogous major fragment ions to their respective product ions conferred the necessary specificity to allow direct analysis of plasma extracts without the need for a chromatographic separation step. Calibration graphs constructed from spiked blank plasma were linear over the range 25-1000 pg ml-1 for each isotopomer, with an overall coefficient of variation of 4.82% and 4.72% for fluphenazine and [2H4] fluphenazine, respectively. The limit of detection was 5 pg ml-1 when 1 ml of plasma was used. The described procedure provided sufficient sensitivity and selectivity such that plasma concentrations of fluphenazine and [2H4] fluphenazine could be followed in schizophrenic patients for 24 h after the simultaneous administration of single oral doses that contain 5 mg each of fluphenazine dihydrochloride and its deuterated isotopomer, [2H4] fluphenazine dihydrochloride. Endogeneous plasma constituents and known metabolites of fluphenazine did not interfere in the assay. Virtually superimposable plasma concentration versus time profiles were obtained, demonstrating that the deuterated isotopomer has no significant isotopic effect.
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