Determination of fluoxetine and norfluoxetine in human plasma by high-performance liquid chromatography with ultraviolet detection in psychiatric patients.
A rapid high-performance liquid chromatographic method is described for the simultaneous determination of the widely used antidepressant drug, fluoxetine and its principal metabolite norfluoxetine in plasma. After liquid-liquid extraction the compounds were separated in a reversed-phase column and assayed by ultraviolet absorption at 226 nm. The analytical interference from psychoactive drugs and their metabolites was also studied. The extraction recoveries were 93 and 87% for norfluoxetine and fluoxetine, respectively. The limit of quantitation under the described conditions was 14 nmol/l for both compounds. The method was found to be reproducible with coefficients of variation less than 10%. A great variability in plasma concentrations of fluoxetine and norfluoxetine as well as in fluoxetine/norfluoxetine ratios was found among the 29 patients studied. This result suggests the implication of genetically polymorphic enzymes, presumably CYP2D6, CYP2C9 and CYP2C19 in the metabolism of fluoxetine to norfluoxetine. Therapeutic drug monitoring should thus be useful in patients treated with regular doses.
LLerena
Adrián
A
Department of Pharmacology, Faculty of Medicine, University of Extremadura, Mérida, Spain. allerena@unex.es
Dorado
Pedro
P
Berecz
Roland
R
González
Antonio
A
Jesús Norberto
María
M
de la Rubia
Alfredo
A
Cáceres
Macarena
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D005473:Fluoxetine; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; C036139:norfluoxetine