SIMULTANEOUS DETERMINATION OF PLASMA-LEVELS OF FLUVOXAMINE AND OF THEENANTIOMERS OF FLUOXETINE AND NORFLUOXETINE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A gas chromatographic-mass spectrometric method is presented which all ows the simultaneous determination of the plasma concentrations of flu voxamine and of the enantiomers of fluoxetine and norfluoxetine after derivatization with the chiral reagent, (S)-(-)-N-trifluoroacetylproly l chloride. No interference was observed from endogenous compounds fol lowing the extraction of plasma samples from six different human subje cts. The standard curves were linear over a working range of 10 to 750 ng/ml for racemic fluoxetine and norfluoxetine and of 50 to 500 ng/ml for fluvoxamine. Recoveries ranged from 50 to 66% for the three compo unds. Intra- and inter-day coefficients of variation ranged from 4 to 10% for fluvoxamine and from 4 to 13% for fluoxetine and norfluoxetine . The limits of quantitation of the method were found to be 2 ng/ml fo r fluvoxamine and 1 ng/ml for the (R)- and (S)-enantiomers of fluoxeti ne and norfluoxetine, hence allowing its use for single dose pharmacok inetics. Finally, by using a steeper gradient of temperature, much sho rter analysis times are obtained if one is interested in the concentra tions of fluvoxamine alone.