SIMULTANEOUS QUANTIFICATION OF FLUOXETINE, NORFLUOXETINE, AND DESIPRAMINE USING GAS-CHROMATOGRAPHY WITH NITROGEN-PHOSPHORUS DETECTION

The combination of fluoxetine (FLU) and desipramine (DMI) has been rep orted to be useful for the treatment of depression, and these drugs ar e also known to undergo a metabolic drug-drug interaction because of t heir effects on cytochrome P-450 2D6. A procedure that separates these two drugs and norfluoxetine (NFLU), the N-demethylated metabolite of FLU, and that allows simultaneous quantification of their levels would be of value and has been developed in our laboratories. The procedure involves an initial extraction into ethyl acetate after basification of the homogenate. The organic phase is retained and taken to dryness; the residue is reconstituted in water and acetylated with acetic anhy dride under slightly basic conditions. Ethyl acetate is then used to e xtract the acetylated compounds from the aqueous medium. The organic l ayer is taken to dryness and the residue reconstituted in toluene. An aliquot of the solution in toluene is injected directly into a gas chr omatograph equipped with a nitrogen-phosphorus detector, a fused silic a capillary column, and an integrator/printer. Maprotiline is added to the initial homogenate and carried through the procedure as the inter nal standard. The assay is rapid and sensitive and has been applied su ccessfully to liver and brain tissue taken from rats treated with FLU, DMI, or the combination.