Liquid chromatographic-mass spectrometric method for the determination of fluoxetine and norfluoxetine in human plasma: Application to clinical study
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A selective, sensitive, simple, and rapid method for the simultaneous determination of fluoxetine (FL) and norfluoxetine (nor-FL) was developed and validated, and further applied to analyze plasma samples obtained from FL-treated patients with Parkinson disease (n:=:18). After one step liquid-liquid extraction with ethyl acetate, plasma samples were chromatographed on a C8 column. The mobile phase was acetate buffer and acetonitrile (40:60 v/v). Determination of FL and nor-FL was performed with MS detection in selective ion monitoring (SIM) mode, so the other components did not interfere with this assay. FL, nor-FL and flumazenil as internal standard were eluted in 6:min. Recoveries ranged from 89.7 to 96.6% and from 80.2 to 85.3% for FL and nor-FL, respectively. The limit of quantitation under described conditions was 2,5 μg/l for FL and 10 μg/l for nor-FL. The method was found to be reproducible with coefficient of variation less than 9%. The parameters of the method were found to be... acceptable to enable its routine use for clinical studies. The method was employed to analyze the Parkinsonian patients' plasma samples. A great deviation in plasma concentrations of FL and nor-FL found among 18 studied patients indicates high pharmacokinetic variability of the drug. Obtained results also indicate absence of the influence of Parkinson disease on the drug disposition.
Keywords:Fluoxetine / High performance liquid chromatography / Mass spectrometry / Norfluoxetine / Pharmacokinetics
Source:Farmaco, 2005, 60, 4, 345-349
- Elsevier Masson SAS